The role of RNA processing in the pathogenesis of motor neuron degeneration

Dirk Bäumer; Olaf Ansorge; Mara Almeida; Kevin Talbot

doi:10.1017/S1462399410001523

The role of RNA processing in the pathogenesis of motor neuron degeneration

Published online by Cambridge University Press: 20 July 2010

Mara Almeida and

Dirk Bäumer: Affiliation:
MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, OX1 3QX, UK. Department of Clinical Neurology, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
Olaf Ansorge: Affiliation:
Department of Neuropathology, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
Mara Almeida: Affiliation:
MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, OX1 3QX, UK.
Kevin Talbot*: Affiliation:
MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, OX1 3QX, UK. Department of Clinical Neurology, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
*: *Corresponding author: Kevin Talbot, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK. E-mail: [email protected]

Article contents

Abstract
References

Get access

Rights & Permissions

Abstract

Motor neurons are large, highly polarised cells with very long axons and a requirement for precise spatial and temporal gene expression. Neurodegenerative disorders characterised by selective motor neuron vulnerability include various forms of amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). A rapid expansion in knowledge on the pathophysiology of motor neuron degeneration has occurred in recent years, largely through the identification of genes leading to familial forms of ALS and SMA. The major emerging theme is that motor neuron degeneration can result from mutation in genes that encode factors important for ribonucleoprotein biogenesis and RNA processing, including splicing regulation, transcript stabilisation, translational repression and localisation of mRNA. Complete understanding of how these pathways interact and elucidation of specialised mechanisms for mRNA targeting and processing in motor neurons are likely to produce new targets for therapy in ALS and related disorders.

Type: Review Article
Information: Expert Reviews in Molecular Medicine , Volume 12 , January 2010 , e21

DOI: https://doi.org/10.1017/S1462399410001523 [Opens in a new window]
Copyright: Copyright © Cambridge University Press 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1Lefebvre, S. et al. (1995) Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80, 155-165CrossRef Google Scholar PubMed

2Rosen, D.R. et al. (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362, 59-62CrossRef Google Scholar PubMed

3Turner, B.J. and Talbot, K. (2008) Transgenics, toxicity and therapeutics in rodent models of mutant SOD1-mediated familial ALS. Progress in Neurobiology 85, 94-134CrossRef Google Scholar PubMed

4Cleveland, D.W. and Rothstein, J.D. (2001) From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nature Reviews Neuroscience 2, 806-819CrossRef Google Scholar PubMed

5Shaw, P.J. (2005) Molecular and cellular pathways of neurodegeneration in motor neurone disease. Journal of Neurology Neurosurgery and Psychiatry 76, 1046-1057CrossRef Google Scholar PubMed

6Neumann, M. et al. (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314, 130-133CrossRef Google Scholar PubMed

7Mackenzie, I.R. et al. (2007) Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations. Annals of Neurology 61, 427-434CrossRef Google Scholar PubMed

8Sreedharan, J. et al. (2008) TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis. Science 319, 1668-1672CrossRef Google Scholar PubMed

9Vance, C. et al. (2009) Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323, 1208-1211CrossRef Google Scholar PubMed

10Licatalosi, D.D. and Darnell, R.B (2010) RNA processing and its regulation: global insights into biological networks. Nature Reviews Genetics 11, 75-87CrossRef Google Scholar PubMed

11Ulfhake, B. and Kellerth, J.O. (1981) A quantitative light microscopic study of the dendrites of cat spinal alpha-motoneurons after intracellular staining with horseradish peroxidase. Journal of Comparative Neurology 202, 571-583CrossRef Google Scholar PubMed

12Lemon, R.N. (2008) Descending pathways in motor control. Annual Review of Neuroscience 31, 195-218CrossRef Google Scholar PubMed

13Eisen, A. (2009) Amyotrophic lateral sclerosis-Evolutionary and other perspectives. Muscle and Nerve 40, 297-304CrossRef Google Scholar PubMed

14Pearn, J. (1978) Incidence, prevalence, and gene frequency studies of chronic childhood spinal muscular atrophy. Journal of Medical Genetics 15, 409-413CrossRef Google Scholar PubMed

15Lefebvre, S. et al. (1997) Correlation between severity and SMN protein level in spinal muscular atrophy. Nature Genetics 16, 265-269CrossRef Google Scholar PubMed

16Schrank, B. et al. (1997) Inactivation of the survival motor neuron gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos. Proceedings of the National Academy of Sciences of the United States of America 94, 9920-9925CrossRef Google Scholar PubMed

17Cartegni, L., Chew, S.L. and Krainer, A.R. (2002) Listening to silence and understanding nonsense: exonic mutations that affect splicing. Nature Reviews Genetics 3, 285-298CrossRef Google Scholar PubMed

18Kashima, T. and Manley, J.L. (2003) A negative element in SMN2 exon 7 inhibits splicing in spinal muscular atrophy. Nature Genetics 34, 460-463CrossRef Google Scholar PubMed

19Monani, U.R. et al. (1999) A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Human Molecular Genetics 8, 1177-1183CrossRef Google Scholar PubMed

20Lorson, C.L. et al. (1999) A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proceedings of the National Academy of Sciences of the United States of America 96, 6307-6311CrossRef Google Scholar PubMed

21Wirth, B. et al. (1997) Different entities of proximal spinal muscular atrophy within one family. Human Genetics 100, 676-680CrossRef Google Scholar PubMed

22Oprea, G.E. et al. (2008) Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy. Science 320, 524-527CrossRef Google Scholar PubMed

23McDermott, C.J. and Shaw, P.J. (2008) Diagnosis and management of motor neurone disease. British Medical Journal 336, 658-662CrossRef Google Scholar PubMed

24Wijesekera, L.C. and Leigh, P.N. (2009) Amyotrophic lateral sclerosis. Orphanet Journal of Rare Diseases 4, 3CrossRef Google Scholar PubMed

25Strong, M.J. (2008) The syndromes of frontotemporal dysfunction in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis 9, 323-338CrossRef Google Scholar PubMed

26Mackenzie, I.R. and Feldman, H.H. (2005) Ubiquitin immunohistochemistry suggests classic motor neuron disease, motor neuron disease with dementia, and frontotemporal dementia of the motor neuron disease type represent a clinicopathologic spectrum. Journal of Neuropathology and Experimental Neurology 64, 730-739CrossRef Google Scholar PubMed

27Neary, D., Snowden, J.S. and Mann, D.M. (2000) Cognitive change in motor neurone disease/amyotrophic lateral sclerosis (MND/ALS). Journal of the Neurological Sciences 180, 15-20CrossRef Google Scholar PubMed

28Arai, T. et al. (2006) TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochemical and Biophysical Research Communications 351, 602-611CrossRef Google Scholar PubMed

29Gitcho, M.A. et al. (2008) TDP-43 A315T mutation in familial motor neuron disease. Annals of Neurology 63, 535-538CrossRef Google Scholar PubMed

30Borroni, B. et al. (2009) Mutation within TARDBP leads to Frontotemporal Dementia without motor neuron disease. Human Mutation 30, E974-983CrossRef Google Scholar PubMed

31Chiò, A et al. (2008) Prevalence of SOD1 mutations in the Italian ALS population. Neurology. 70, 533–7CrossRef Google Scholar PubMed

32O'Toole, O. et al. (2008) Epidemiology and clinical features of amyotrophic lateral sclerosis in Ireland between 1995 and 2004. Journal of Neurology Neurosurgery and Psychiatry 79, 30-32CrossRef Google Scholar PubMed

33Greenway, M.J. et al. (2006) ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis. Nature Genetics 38, 411-413CrossRef Google Scholar PubMed

34Schymick, J.C., Talbot, K. and Traynor, B.J. (2007) Genetics of sporadic amyotrophic lateral sclerosis. Human Molecular Genetics 16 Spec No. 2, R233-242CrossRef Google Scholar

35Ravits, J.M. and La Spada, A.R. (2009) ALS motor phenotype heterogeneity, focality, and spread: deconstructing motor neuron degeneration. Neurology 73, 805-811CrossRef Google Scholar PubMed

36James, P.A. and Talbot, K. (2006) The molecular genetics of non-ALS motor neuron diseases. Biochimica et Biophysica Acta 1762, 986-1000CrossRef Google Scholar PubMed

37Lee, C.J. and Irizarry, K. (2003) Alternative splicing in the nervous system: an emerging source of diversity and regulation. Biological Psychiatry 54, 771-776CrossRef Google Scholar PubMed

38Li, Q., Lee, J.A. and Black, D.L. (2007) Neuronal regulation of alternative pre-mRNA splicing. Nature Reviews Neuroscience 8, 819-831CrossRef Google Scholar PubMed

39Wojtowicz, W.M. et al. (2004) Alternative splicing of Drosophila Dscam generates axon guidance receptors that exhibit isoform-specific homophilic binding. Cell 118, 619-633CrossRef Google Scholar PubMed

40Matthews, B.J. et al. (2007) Dendrite self-avoidance is controlled by Dscam. Cell 129, 593-604CrossRef Google Scholar PubMed

41Boucard, A.A. et al. (2005) A splice code for trans-synaptic cell adhesion mediated by binding of neuroligin 1 to alpha- and beta-neurexins. Neuron 48, 229-236CrossRef Google Scholar PubMed

42Chih, B., Engelman, H. and Scheiffele, P. (2005) Control of excitatory and inhibitory synapse formation by neuroligins. Science 307, 1324-1328CrossRef Google Scholar PubMed

43Chih, B., Gollan, L. and Scheiffele, P. (2006) Alternative splicing controls selective trans-synaptic interactions of the neuroligin-neurexin complex. Neuron 51, 171-178CrossRef Google Scholar PubMed

44Raingo, J., Castiglioni, A.J. and Lipscombe, D. (2007) Alternative splicing controls G protein-dependent inhibition of N-type calcium channels in nociceptors. Nature Neuroscience 10, 285-292CrossRef Google Scholar PubMed

45Wahl, M.C., Will, C.L. and Luhrmann, R. (2009) The spliceosome: design principles of a dynamic RNP machine. Cell 136, 701-718CrossRef Google Scholar PubMed

46Will, C.L. and Luhrmann, R. (2005) Splicing of a rare class of introns by the U12-dependent spliceosome. Biological Chemistry 386, 713-724CrossRef Google Scholar PubMed

47Meister, G. et al. (2001) A multiprotein complex mediates the ATP-dependent assembly of spliceosomal U snRNPs. Nature Cell Biology 3, 945-949CrossRef Google Scholar PubMed

48Pellizzoni, L., Yong, J. and Dreyfuss, G. (2002) Essential role for the SMN complex in the specificity of snRNP assembly. Science 298, 1775-1779CrossRef Google Scholar PubMed

49Yang, Y.Y., Yin, G.L. and Darnell, R.B. (1998) The neuronal RNA-binding protein Nova-2 is implicated as the autoantigen targeted in POMA patients with dementia. Proceedings of the National Academy of Sciences of the United States of America 95, 13254-13259CrossRef Google Scholar PubMed

50Jensen, K.B. et al. (2000) Nova-1 regulates neuron-specific alternative splicing and is essential for neuronal viability. Neuron 25, 359-371CrossRef Google Scholar PubMed

51Ule, J. et al. (2006) An RNA map predicting Nova-dependent splicing regulation. Nature 444, 580-586CrossRef Google Scholar PubMed

52Ule, J. et al. (2005) Nova regulates brain-specific splicing to shape the synapse. Nature Genetics 37, 844-852CrossRef Google Scholar PubMed

53Ruggiu, M. et al. (2009) Rescuing Z+ agrin splicing in Nova null mice restores synapse formation and unmasks a physiologic defect in motor neuron firing. Proceedings of the National Academy of Sciences of the United States of America 106, 3513-3518CrossRef Google Scholar PubMed

54Buratti, E. and Baralle, F.E. (2001) Characterization and functional implications of the RNA binding properties of nuclear factor TDP-43, a novel splicing regulator of CFTR exon 9. Journal of Biological Chemistry 276, 36337-36343CrossRef Google Scholar PubMed

55Buratti, E. et al. (2001) Nuclear factor TDP-43 and SR proteins promote in vitro and in vivo CFTR exon 9 skipping. EMBO Journal 20, 1774-1784CrossRef Google Scholar PubMed

56Buratti, E. et al. (2004) Nuclear factor TDP-43 binds to the polymorphic TG repeats in CFTR intron 8 and causes skipping of exon 9: a functional link with disease penetrance. American Journal of Human Genetics 74, 1322-1325CrossRef Google Scholar

57Ayala, Y.M., Pagani, F. and Baralle, F.E. (2006) TDP43 depletion rescues aberrant CFTR exon 9 skipping. FEBS Letters 580, 1339-1344CrossRef Google Scholar PubMed

58Mercado, P.A. et al. (2005) Depletion of TDP 43 overrides the need for exonic and intronic splicing enhancers in the human apoA-II gene. Nucleic Acids Research 33, 6000-6010CrossRef Google Scholar PubMed

59D'Ambrogio, A. et al. (2009) Functional mapping of the interaction between TDP-43 and hnRNP A2 in vivo. Nucleic Acids Res 37, 4116-4126CrossRef Google Scholar PubMed

60Ayala, Y.M., Misteli, T. and Baralle, F.E. (2008) TDP-43 regulates retinoblastoma protein phosphorylation through the repression of cyclin-dependent kinase 6 expression. Proceedings of the National Academy of Sciences of the United States of America 105, 3785-3789CrossRef Google Scholar PubMed

61Bose, J.K. et al. (2008) TDP-43 overexpression enhances exon 7 inclusion during the survival of motor neuron pre-mRNA splicing. Journal of Biological Chemistry 283, 28852-28859CrossRef Google Scholar PubMed

62Iko, Y. et al. (2004) Domain architectures and characterization of an RNA-binding protein, TLS. Journal of Biological Chemistry 279, 44834-44840CrossRef Google Scholar PubMed

63Yang, L. et al. (1998) Oncoprotein TLS interacts with serine-arginine proteins involved in RNA splicing. Journal of Biological Chemistry 273, 27761-27764CrossRef Google Scholar PubMed

64Meissner, M. et al. (2003) Proto-oncoprotein TLS/FUS is associated to the nuclear matrix and complexed with splicing factors PTB, SRm160, and SR proteins. Experimental Cell Research 283, 184-195CrossRef Google Scholar

65Sato, S. et al. (2005) beta-catenin interacts with the FUS proto-oncogene product and regulates pre-mRNA splicing. Gastroenterology 129, 1225-1236CrossRef Google Scholar PubMed

66Yang, L., Embree, L.J. and Hickstein, D.D. (2000) TLS-ERG leukemia fusion protein inhibits RNA splicing mediated by serine-arginine proteins. Molecular and Cellular Biology 20, 3345-3354CrossRef Google Scholar PubMed

67Lerga, A. et al. (2001) Identification of an RNA binding specificity for the potential splicing factor TLS. Journal of Biological Chemistry 276, 6807-6816CrossRef Google Scholar PubMed

68Davidson, Y. et al. (2007) Ubiquitinated pathological lesions in frontotemporal lobar degeneration contain the TAR DNA-binding protein, TDP-43. Acta Neuropathologica 113, 521-533CrossRef Google Scholar PubMed

69Cairns, N.J. et al. (2007) TDP-43 in familial and sporadic frontotemporal lobar degeneration with ubiquitin inclusions. American Journal of Pathology 171, 227-240CrossRef Google Scholar PubMed

70Kwiatkowski, T.J. Jr. et al. (2009) Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323, 1205-1208CrossRef Google Scholar PubMed

71Neumann, M. et al. (2009) A new sub-type of frontotemporal lobar degeneration with FUS pathology. Brain 132, 2922-2931CrossRef Google Scholar

72Feiguin, F. et al. (2009) Depletion of TDP-43 affects Drosophila motoneurons terminal synapsis and locomotive behavior. FEBS Lett 583, 1586-1592CrossRef Google Scholar PubMed

73Andersson, M.K. et al. (2008) The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response. BMC Cell Biology 9, 37CrossRef Google Scholar PubMed

74Aman, P. et al. (1996) Expression patterns of the human sarcoma-associated genes FUS and EWS and the genomic structure of FUS. Genomics 37, 1-8CrossRef Google Scholar PubMed

75Gabanella, F. et al. (2005) The activity of the spinal muscular atrophy protein is regulated during development and cellular differentiation. Human Molecular Genetics 14, 3629-3642CrossRef Google Scholar PubMed

76Gabanella, F. et al. (2007) Ribonucleoprotein assembly defects correlate with spinal muscular atrophy severity and preferentially affect a subset of spliceosomal snRNPs. PLoS One 2, e921CrossRef Google Scholar PubMed

77Zhang, Z. et al. (2008) SMN deficiency causes tissue-specific perturbations in the repertoire of snRNAs and widespread defects in splicing. Cell 133, 585-600CrossRef Google Scholar PubMed

78Baumer, D. et al. (2009) Alternative splicing events are alte feature of pathology ina mouse model of spinal muscular atrophy. PLoS Genetics 5, e1000773.CrossRef Google Scholar

79Xiao, S. et al. (2008) An aggregate-inducing peripherin isoform generated through intron retention is upregulated in amyotrophic lateral sclerosis and associated with disease pathology. Journal of Neuroscience 28, 1833-1840CrossRef Google Scholar PubMed

80Rabin, S. et al. (2010) Sporadic ALS has compartment-specific aberrant exon splicing and altered cell-matrix adhesion biology. Human Molecular Genetics 19, 313-328CrossRef Google Scholar PubMed

81Martin, K.C. and Zukin, R.S. (2006) RNA trafficking and local protein synthesis in dendrites: an overview. Journal of Neuroscience 26, 7131-7134CrossRef Google Scholar PubMed

82Giorgi, C. and Moore, M.J. (2007) The nuclear nurture and cytoplasmic nature of localized mRNPs. Seminars in Cell and Developmental Biology 18, 186-193CrossRef Google Scholar PubMed

83Oleynikov, Y. and Singer, R.H. (2003) Real-time visualization of ZBP1 association with beta-actin mRNA during transcription and localization. Current Biology 13, 199-207CrossRef Google Scholar PubMed

84di Penta, A. et al. (2009) Dendritic LSm1/CBP80-mRNPs mark the early steps of transport commitment and translational control. Journal of Cell Biology 184, 423-435CrossRef Google Scholar PubMed

85Gu, W. et al. (2002) A predominantly nuclear protein affecting cytoplasmic localization of beta-actin mRNA in fibroblasts and neurons. Journal of Cell Biology 156, 41-51CrossRef Google Scholar PubMed

86Ross, A.F. et al. (1997) Characterization of a beta-actin mRNA zipcode-binding protein. Molecular and Cellular Biology 17, 2158-2165CrossRef Google Scholar PubMed

87Condeelis, J. and Singer, R.H. (2005) How and why does beta-actin mRNA target? Biology of the Cell 97, 97-110CrossRef Google Scholar PubMed

88Tiruchinapalli, D.M. et al. (2003) Activity-dependent trafficking and dynamic localization of zipcode binding protein 1 and beta-actin mRNA in dendrites and spines of hippocampal neurons. Journal of Neuroscience 23, 3251-3261CrossRef Google Scholar PubMed

89Zhang, H.L. et al. (2001) Neurotrophin-induced transport of a beta-actin mRNP complex increases beta-actin levels and stimulates growth cone motility. Neuron 31, 261-275CrossRef Google Scholar PubMed

90Knowles, R.B. et al. (1996) Translocation of RNA granules in living neurons. Journal of Neuroscience 16, 7812-7820CrossRef Google Scholar PubMed

91Krichevsky, A.M. and Kosik, K.S. (2001) Neuronal RNA granules: a link between RNA localization and stimulation-dependent translation. Neuron 32, 683-696CrossRef Google Scholar PubMed

92Kiebler, M.A. and Bassell, G.J. (2006) Neuronal RNA granules: movers and makers. Neuron 51, 685-690CrossRef Google Scholar PubMed

93Martin, K.C. and Ephrussi, A. (2009) mRNA localization: gene expression in the spatial dimension. Cell 136, 719-730CrossRef Google Scholar PubMed

94Elvira, G. et al. (2006) Characterization of an RNA granule from developing brain. Molecular and Cellular Proteomics 5, 635-651CrossRef Google Scholar PubMed

95Kiebler, M.A. et al. (1999) The mammalian staufen protein localizes to the somatodendritic domain of cultured hippocampal neurons: implications for its involvement in mRNA transport. Journal of Neuroscience 19, 288-297CrossRef Google Scholar

96Kanai, Y., Dohmae, N. and Hirokawa, N. (2004) Kinesin transports RNA: isolation and characterization of an RNA-transporting granule. Neuron 43, 513-525CrossRef Google Scholar PubMed

97Landers, J.E. et al. (2009) Reduced expression of the Kinesin-Associated Protein 3 (KIFAP3) gene increases survival in sporadic amyotrophic lateral sclerosis. Proceedings of the National Academy of Sciences of the United States of America 106, 9004-9009CrossRef Google Scholar PubMed

98Munch, C. et al. (2004) Point mutations of the p150 subunit of dynactin (DCTN1) gene in ALS. Neurology 63, 724-726CrossRef Google Scholar PubMed

99Munch, C. et al. (2005) Heterozygous R1101K mutation of the DCTN1 gene in a family with ALS and FTD. Annals of Neurology 58, 777-780CrossRef Google Scholar

100Puls, I. et al. (2003) Mutant dynactin in motor neuron disease. Nature Genetics 33, 455-456CrossRef Google Scholar PubMed

101Fujii, R. et al. (2005) The RNA binding protein TLS is translocated to dendritic spines by mGluR5 activation and regulates spine morphology. Current Biology 15, 587-593CrossRef Google Scholar PubMed

102Fujii, R. and Takumi, T. (2005) TLS facilitates transport of mRNA encoding an actin-stabilizing protein to dendritic spines. Journal of Cell Science 118, 5755-5765CrossRef Google Scholar PubMed

103Yoshimura, A. et al. (2006) Myosin-Va facilitates the accumulation of mRNA/protein complex in dendritic spines. Current Biology 16, 2345-2351CrossRef Google Scholar PubMed

104Fan, L. and Simard, L.R. (2002) Survival motor neuron (SMN) protein: role in neurite outgrowth and neuromuscular maturation during neuronal differentiation and development. Human Molecular Genetics 11, 1605-1614CrossRef Google Scholar PubMed

105Rossoll, W. et al. (2002) Specific interaction of Smn, the spinal muscular atrophy determining gene product, with hnRNP-R and gry-rbp/hnRNP-Q: a role for Smn in RNA processing in motor axons? Human Molecular Genetics 11, 93-105CrossRef Google Scholar PubMed

106Jablonka, S. et al. (2001) Co-regulation of survival of motor neuron (SMN) protein and its interactor SIP1 during development and in spinal muscular atrophy. Human Molecular Genetics 10, 497-505CrossRef Google Scholar PubMed

107Bechade, C. et al. (1999) Subcellular distribution of survival motor neuron (SMN) protein: possible involvement in nucleocytoplasmic and dendritic transport. European Journal of Neuroscience 11, 293-304CrossRef Google Scholar PubMed

108Pagliardini, S. et al. (2000) Subcellular localization and axonal transport of the survival motor neuron (SMN) protein in the developing rat spinal cord. Human Molecular Genetics 9, 47-56CrossRef Google Scholar PubMed

109Briese, M. et al. (2006) SMN, the product of the spinal muscular atrophy-determining gene, is expressed widely but selectively in the developing human forebrain. Journal of Comparative Neurology 497, 808-816CrossRef Google Scholar PubMed

110Giavazzi, A. et al. (2006) Neuronal-specific roles of the survival motor neuron protein: evidence from survival motor neuron expression patterns in the developing human central nervous system. Journal of Neuropathology and Experimental Neurology 65, 267-277CrossRef Google Scholar PubMed

111Rossoll, W. and Bassell, GJ (2009) Spinal muscular atrophy and a model for survival of motor neuron protein function in axonal ribonucleoprotein complexes. Results and Problems in Cell Differentiation. 48, 289-326Google Scholar

112McWhorter, M.L. et al. (2003) Knockdown of the survival motor neuron (Smn) protein in zebrafish causes defects in motor axon outgrowth and pathfinding. Journal of Cell Biology 162, 919-931CrossRef Google Scholar PubMed

113Rossoll, W. et al. (2003) Smn, the spinal muscular atrophy-determining gene product, modulates axon growth and localization of beta-actin mRNA in growth cones of motoneurons. Journal of Cell Biology 163, 801-812CrossRef Google Scholar PubMed

114Zhang, H. et al. (2006) Multiprotein complexes of the survival of motor neuron protein SMN with Gemins traffic to neuronal processes and growth cones of motor neurons. Journal of Neuroscience 26, 8622-8632CrossRef Google Scholar PubMed

115Meister, G., Eggert, C. and Fischer, U. (2002) SMN-mediated assembly of RNPs: a complex story. Trends in Cell Biology 12, 472-478CrossRef Google Scholar PubMed

116Luo, L. (2002) Actin cytoskeleton regulation in neuronal morphogenesis and structural plasticity. Annual Review of Cell and Developmental Biology 18, 601-635CrossRef Google Scholar PubMed

117Strong, M.J. et al. (2007) TDP43 is a human low molecular weight neurofilament (hNFL) mRNA-binding protein. Molecular and Cellular Neurosciences 35, 320-327CrossRef Google Scholar PubMed

118Wang, I.F. et al. (2008) TDP-43, the signature protein of FTLD-U, is a neuronal activity-responsive factor. Journal of Neurochemistry 105, 797-806CrossRef Google Scholar PubMed

119Lu, L. et al. (2007) Mutant Cu/Zn-superoxide dismutase associated with amyotrophic lateral sclerosis destabilizes vascular endothelial growth factor mRNA and downregulates its expression. Journal of Neuroscience 27, 7929-7938CrossRef Google Scholar PubMed

120Li, X. et al. (2009) Mutant copper-zinc superoxide dismutase associated with amyotrophic lateral sclerosis binds to adenine/uridine-rich stability elements in the vascular endothelial growth factor 3'-untranslated region. Journal of Neurochemistry 108, 1032-1044CrossRef Google Scholar PubMed

121Ge, W.W. et al. (2005) Mutant copper-zinc superoxide dismutase binds to and destabilizes human low molecular weight neurofilament mRNA. Journal of Biological Chemistry 280, 118-124CrossRef Google Scholar PubMed

122Volkening, K. et al. (2009) Tar DNA binding protein of 43 kDa (TDP-43), 14–3-3 proteins and copper/zinc superoxide dismutase (SOD1) interact to modulate NFL mRNA stability. Implications for altered RNA processing in amyotrophic lateral sclerosis (ALS). Brain Research 1305, 168-182CrossRef Google Scholar PubMed

123Besse, F. and Ephrussi, A. (2008) Translational control of localized mRNAs: restricting protein synthesis in space and time. Nature Reviews Molecular Cell Biology 9, 971-980CrossRef Google Scholar PubMed

124Napoli, I. et al. (2008) The fragile X syndrome protein represses activity-dependent translation through CYFIP1, a new 4E-BP. Cell 134, 1042-1054CrossRef Google Scholar PubMed

125Huttelmaier, S. et al. (2005) Spatial regulation of beta-actin translation by Src-dependent phosphorylation of ZBP1. Nature 438, 512-515CrossRef Google Scholar PubMed

126Huang, Y.S. et al. (2002) N-methyl-D-aspartate receptor signaling results in Aurora kinase-catalyzed CPEB phosphorylation and alpha CaMKII mRNA polyadenylation at synapses. EMBO Journal 21, 2139-2148CrossRef Google Scholar PubMed

127Koenig, E. and Martin, R. (1996) Cortical plaque-like structures identify ribosome-containing domains in the Mauthner cell axon. Journal of Neuroscience 16, 1400-1411CrossRef Google Scholar PubMed

128Koenig, E. et al. (2000) Cryptic peripheral ribosomal domains distributed intermittently along mammalian myelinated axons. Journal of Neuroscience 20, 8390-8400CrossRef Google Scholar PubMed

129Merianda, T.T. et al. (2009) A functional equivalent of endoplasmic reticulum and Golgi in axons for secretion of locally synthesized proteins. Molecular and Cellular Neurosciences 40, 128-142CrossRef Google Scholar PubMed

130Lin, A.C. and Holt, C.E. (2008) Function and regulation of local axonal translation. Current Opinion in Neurobiology 18, 60-68CrossRef Google Scholar PubMed

131Giuditta, A. et al. (2008) Local gene expression in axons and nerve endings: the glia-neuron unit. Physiological Reviews 88, 515-555CrossRef Google Scholar PubMed

132Leung, K.M. et al. (2006) Asymmetrical beta-actin mRNA translation in growth cones mediates attractive turning to netrin-1. Nature Neuroscience 9, 1247-1256CrossRef Google Scholar PubMed

133Lin, A.C. and Holt, C.E. (2007) Local translation and directional steering in axons. EMBO Journal 26, 3729-3736CrossRef Google Scholar PubMed

134Hanz, S. et al. (2003) Axoplasmic importins enable retrograde injury signaling in lesioned nerve. Neuron 40, 1095-1104CrossRef Google Scholar PubMed

135Yudin, D. et al. (2008) Localized regulation of axonal RanGTPase controls retrograde injury signaling in peripheral nerve. Neuron 59, 241-252CrossRef Google Scholar PubMed

136Taylor, A.M. et al. (2009) Axonal mRNA in uninjured and regenerating cortical mammalian axons. Journal of Neuroscience 29, 4697-4707CrossRef Google Scholar PubMed

137Willis, D. et al. (2005) Differential transport and local translation of cytoskeletal, injury-response, and neurodegeneration protein mRNAs in axons. Journal of Neuroscience 25, 778-791CrossRef Google Scholar PubMed

138Jimenez-Diaz, L. et al. (2008) Local translation in primary afferent fibers regulates nociception. PLoS One 3, e1961CrossRef Google Scholar PubMed

139Yoo, S. et al. (2010) Dynamics of axonal mRNA transport and implications for peripheral nerve regeneration. Experimental Neurology 223, 19-27CrossRef Google Scholar PubMed

140Antonellis, A. et al. (2003) Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V. American Journal of Human Genetics 72, 1293-1299CrossRef Google Scholar PubMed

141Jordanova, A. et al. (2006) Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy. Nature Genetics 38, 197-202CrossRef Google Scholar PubMed

142Antonellis, A. and Green, E.D. (2008) The role of aminoacyl-tRNA synthetases in genetic diseases. Annual Review of Genomics and Human Genetics 9, 87-107CrossRef Google Scholar PubMed

143Motley, W., Talbot, K. and Fischbeck, K. (2010) GARS axonopathy - not every neuron's cup of tRNA Trends in Neuroscience 33, 59-66CrossRef Google Scholar

144Chihara, T., Luginbuhl, D. and Luo, L. (2007) Cytoplasmic and mitochondrial protein translation in axonal and dendritic terminal arborization. Nature Neuroscience 10, 828-837CrossRef Google Scholar PubMed

145Grohmann, K. et al. (2001) Mutations in the gene encoding immunoglobulin mu-binding protein 2 cause spinal muscular atrophy with respiratory distress type 1. Nature Genetics 29, 75-77CrossRef Google Scholar PubMed

146Grohmann, K. et al. (2004) Characterization of Ighmbp2 in motor neurons and implications for the pathomechanism in a mouse model of human spinal muscular atrophy with respiratory distress type 1 (SMARD1). Human Molecular Genetics 13, 2031-2042CrossRef Google Scholar

147Guenther, U.P. et al. (2009) IGHMBP2 is a ribosome-associated helicase inactive in the neuromuscular disorder distal SMA type 1 (DSMA1). Human Molecular Genetics 18, 1288-1300CrossRef Google Scholar PubMed

148Chen, Y.Z. et al. (2004) DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4). American Journal of Human Genetics 74, 1128-1135CrossRef Google Scholar

149Suraweera, A. et al. (2007) Senataxin, defective in ataxia oculomotor apraxia type 2, is involved in the defense against oxidative DNA damage. Journal of Cell Biology 177, 969-979CrossRef Google Scholar PubMed

150Suraweera, A. et al. (2009) Functional role for senataxin, defective in ataxia oculomotor apraxia type 2, in transcriptional regulation. Human Molecular Genetics 18, 3384-3396CrossRef Google Scholar PubMed

151Chen, Y.Z. et al. (2006) Senataxin, the yeast Sen1p orthologue: characterization of a unique protein in which recessive mutations cause ataxia and dominant mutations cause motor neuron disease. Neurobiology of Disease 23, 97-108CrossRef Google Scholar PubMed

152Tsai, N.P., Tsui, Y.C. and Wei, L.N. (2009) Dynein motor contributes to stress granule dynamics in primary neurons. Neuroscience 159, 647-656CrossRef Google Scholar PubMed

153DeGracia, D.J. et al. (2007) Convergence of stress granules and protein aggregates in hippocampal cornu ammonis 1 at later reperfusion following global brain ischemia. Neuroscience 146, 562-572CrossRef Google Scholar PubMed

154Anderson, P. and Kedersha, N. (2008) Stress granules: the Tao of RNA triage. Trends in Biochemical Sciences 33, 141-150CrossRef Google Scholar PubMed

155Anderson, P. and Kedersha, N. (2006) RNA granules. Journal of Cell Biology 172, 803-808CrossRef Google Scholar PubMed

156Kawai, T. et al. (2004) Global mRNA stabilization preferentially linked to translational repression during the endoplasmic reticulum stress response. Molecular and Cellular Biology 24, 6773-6787CrossRef Google Scholar PubMed

157Harding, H.P. et al. (2002) Transcriptional and translational control in the Mammalian unfolded protein response. Annual Review of Cell and Developmental Biology 18, 575-599CrossRef Google Scholar PubMed

158Harding, H.P. et al. (2003) An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Molecular Cell 11, 619-633CrossRef Google Scholar PubMed

159Kedersha, N. et al. (2002) Evidence that ternary complex (eIF2-GTP-tRNA(i)(Met))-deficient preinitiation complexes are core constituents of mammalian stress granules. Molecular Biology of the Cell 13, 195-210CrossRef Google Scholar

160Ayala, Y.M. et al. (2008) Structural determinants of the cellular localization and shuttling of TDP-43. Journal of Cell Science 121, 3778-3785CrossRef Google Scholar PubMed

161Zinszner, H. et al. (1997) TLS (FUS) binds RNA in vivo and engages in nucleo-cytoplasmic shuttling. Journal of Cell Science 110, 1741-1750CrossRef Google Scholar PubMed

162Kedersha, N. et al. (2000) Dynamic shuttling of TIA-1 accompanies the recruitment of mRNA to mammalian stress granules. Journal of Cell Biology 151, 1257-1268CrossRef Google Scholar PubMed

163Taupin, J.L. et al. (1995) The RNA-binding protein TIAR is translocated from the nucleus to the cytoplasm during Fas-mediated apoptotic cell death. Proceedings of the National Academy of Sciences of the United States of America 92, 1629-1633CrossRef Google Scholar

164Gallouzi, I.E. et al. (2000) HuR binding to cytoplasmic mRNA is perturbed by heat shock. Proceedings of the National Academy of Sciences of the United States of America 97, 3073-3078CrossRef Google Scholar PubMed

165Moisse, K. et al. (2009) Divergent patterns of cytosolic TDP-43 and neuronal progranulin expression following axotomy: implications for TDP-43 in the physiological response to neuronal injury. Brain Res 1249, 202-211CrossRef Google Scholar PubMed

166Moisse, K. et al. (2009) Cytosolic TDP-43 expression following axotomy is associated with caspase 3 activation in NFL(-/-) mice: Support for a role for TDP-43 in the physiological response to neuronal injury. Brain Res 1296, 176-86CrossRef Google Scholar PubMed

167Colombrita, C. et al. (2009) TDP-43 is recruited to stress granules in conditions of oxidative insult. Journal of Neurochemistry 111, 1051-61CrossRef Google Scholar PubMed

168Fujita, K. et al. (2008) Immunohistochemical identification of messenger RNA-related proteins in basophilic inclusions of adult-onset atypical motor neuron disease. Acta Neuropathol 116, 439-445CrossRef Google Scholar PubMed

169Munoz, D.G. et al. (2009) FUS pathology in basophilic inclusion body disease. Acta Neuropathol 118, 617-627CrossRef Google Scholar PubMed

170McEwen, E. et al. (2005) Heme-regulated inhibitor kinase-mediated phosphorylation of eukaryotic translation initiation factor 2 inhibits translation, induces stress granule formation, and mediates survival upon arsenite exposure. Journal of Biological Chemistry 280, 16925-16933CrossRef Google Scholar PubMed

171Mazroui, R. et al. (2006) Inhibition of ribosome recruitment induces stress granule formation independently of eukaryotic initiation factor 2alpha phosphorylation. Molecular Biology of the Cell 17, 4212-4219CrossRef Google Scholar PubMed

172Yamasaki, S. et al. (2009) Angiogenin cleaves tRNA and promotes stress-induced translational repression. Journal of Cell Biology 185, 35-42CrossRef Google Scholar PubMed

173Gellera, C. et al. (2008) Identification of new ANG gene mutations in a large cohort of Italian patients with amyotrophic lateral sclerosis. Neurogenetics 9, 33-40CrossRef Google Scholar

174Crabtree, B. et al. (2007) Characterization of human angiogenin variants implicated in amyotrophic lateral sclerosis. Biochemistry 46, 11810-11818CrossRef Google Scholar PubMed

175Subramanian, V., Crabtree, B. and Acharya, K.R. (2008) Human angiogenin is a neuroprotective factor and amyotrophic lateral sclerosis associated angiogenin variants affect neurite extension/pathfinding and survival of motor neurons. Human Molecular Genetics 17, 130-149CrossRef Google Scholar PubMed

176Hua, Y. and Zhou, J. (2004) Rpp20 interacts with SMN and is re-distributed into SMN granules in response to stress. Biochemical and Biophysical Research Communications 314, 268-276CrossRef Google Scholar PubMed

177Hua, Y. and Zhou, J. (2004) Survival motor neuron protein facilitates assembly of stress granules. FEBS Lett 572, 69-74CrossRef Google Scholar PubMed

178Cougot, N. et al. (2008) Dendrites of mammalian neurons contain specialized P-body-like structures that respond to neuronal activation. Journal of Neuroscience 28, 13793-13804CrossRef Google Scholar PubMed

179Zeitelhofer, M., Macchi, P. and Dahm, R. (2008) Perplexing bodies: The putative roles of P-bodies in neurons. RNA Biol 5, 244-248CrossRef Google Scholar PubMed

180Zeitelhofer, M. et al. (2008) Dynamic interaction between P-bodies and transport ribonucleoprotein particles in dendrites of mature hippocampal neurons. Journal of Neuroscience 28, 7555-7562CrossRef Google Scholar PubMed

181Brengues, M., Teixeira, D. and Parker, R. (2005) Movement of eukaryotic mRNAs between polysomes and cytoplasmic processing bodies. Science 310, 486-489CrossRef Google Scholar PubMed

182Cougot, N., Babajko, S. and Seraphin, B. (2004) Cytoplasmic foci are sites of mRNA decay in human cells. Journal of Cell Biology 165, 31-40CrossRef Google Scholar PubMed

183Sheth, U. and Parker, R. (2006) Targeting of aberrant mRNAs to cytoplasmic processing bodies. Cell 125, 1095-1109CrossRef Google Scholar PubMed

184Anderson, P. and Kedersha, N. (2009) RNA granules: post-transcriptional and epigenetic modulators of gene expression. Nature Reviews Molecular Cell Biology 10, 430-436CrossRef Google Scholar PubMed

185Parker, R. and Sheth, U. (2007) P bodies and the control of mRNA translation and degradation. Molecular Cell 25, 635-646CrossRef Google Scholar PubMed

186Gregory, R.I. et al. (2004) The Microprocessor complex mediates the genesis of microRNAs. Nature 432, 235-240CrossRef Google Scholar PubMed

187Bicker, S. and Schratt, G. (2008) microRNAs: tiny regulators of synapse function in development and disease. Journal of Cellular and Molecular Medicine 12, 1466-1476CrossRef Google Scholar PubMed

188Carthew, R.W. and Sontheimer, E.J. (2009) Origins and Mechanisms of miRNAs and siRNAs. Cell 136, 642-655CrossRef Google Scholar PubMed

189Kosik, K.S. (2006) The neuronal microRNA system. Nature Reviews Neuroscience 7, 911-920CrossRef Google Scholar PubMed

190Schaefer, A. et al. (2007) Cerebellar neurodegeneration in the absence of microRNAs. Journal of Experimental Medicine 204, 1553-1558CrossRef Google Scholar PubMed

191Damiani, D. et al. (2008) Dicer inactivation leads to progressive functional and structural degeneration of the mouse retina. Journal of Neuroscience 28, 4878-4887CrossRef Google Scholar PubMed

192Kim, J. et al. (2007) A MicroRNA feedback circuit in midbrain dopamine neurons. Science 317, 1220-1224CrossRef Google Scholar PubMed

193Li, X. and Jin, P. (2009) Macro role(s) of microRNAs in fragile X syndrome? Neuromolecular Medicine 11, 200-207CrossRef Google Scholar PubMed

194Abelson, J.F. et al. (2005) Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science 310, 317-320CrossRef Google Scholar PubMed

195Lukiw, W.J. (2007) Micro-RNA speciation in fetal, adult and Alzheimer's disease hippocampus. Neuroreport 18, 297-300CrossRef Google Scholar PubMed

196Bilen, J., Liu, N. and Bonini, N.M. (2006) A new role for microRNA pathways: modulation of degeneration induced by pathogenic human disease proteins. Cell Cycle 5, 2835-2838CrossRef Google Scholar PubMed

197Bilen, J. et al. (2006) MicroRNA pathways modulate polyglutamine-induced neurodegeneration. Molecular Cell 24, 157-163CrossRef Google Scholar PubMed

198Gass, J. et al. (2006) Mutations in progranulin are a major cause of ubiquitin-positive frontotemporal lobar degeneration. Human Molecular Genetics 15, 2988-3001CrossRef Google Scholar

199Rademakers, R. et al. (2008) Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia. Human Molecular Genetics 17, 3631-3642CrossRef Google Scholar

200Bass, B.L. (2002) RNA editing by adenosine deaminases that act on RNA. Annual Review of Biochemistry 71, 817-846CrossRef Google Scholar PubMed

201Greger, I.H. et al. (2003) AMPA receptor tetramerization is mediated by Q/R editing. Neuron 40, 763-774CrossRef Google Scholar PubMed

202Burnashev, N. et al. (1992) Divalent ion permeability of AMPA receptor channels is dominated by the edited form of a single subunit. Neuron 8, 189-198CrossRef Google Scholar PubMed

203Kawahara, Y. et al. (2004) Glutamate receptors: RNA editing and death of motor neurons. Nature 427, 801CrossRef Google Scholar PubMed

204Kwak, S. and Kawahara, Y. (2005) Deficient RNA editing of GluR2 and neuronal death in amyotropic lateral sclerosis. Journal of Molecular Medicine 83, 110-120CrossRef Google Scholar PubMed

205Wamer, W.G., Yin, J.J. and Wei, R.R. (1997) Oxidative damage to nucleic acids photosensitized by titanium dioxide. Free Radical Biology and Medicine 23, 851-858CrossRef Google Scholar PubMed

206Tanaka, M., Chock, P.B. and Stadtman, E.R. (2007) Oxidized messenger RNA induces translation errors. Proceedings of the National Academy of Sciences of the United States of America 104, 66-71CrossRef Google Scholar PubMed

207Shan, X., Chang, Y. and Lin, C.L. (2007) Messenger RNA oxidation is an early event preceding cell death and causes reduced protein expression. FASEB Journal 21, 2753-2764CrossRef Google Scholar PubMed

208Nunomura, A. et al. (2009) RNA oxidation in Alzheimer disease and related neurodegenerative disorders. Acta Neuropathol 118, 151-166CrossRef Google Scholar PubMed

209Chang, Y. et al. (2008) Messenger RNA oxidation occurs early in disease pathogenesis and promotes motor neuron degeneration in ALS. PLoS One 3, e2849CrossRef Google Scholar PubMed

210Strasswimmer, J. et al. (1999) Identification of survival motor neuron as a transcriptional activator-binding protein. Human Molecular Genetics 8, 1219-1226CrossRef Google Scholar PubMed

211Pellizzoni, L. et al. (2001) A functional interaction between the survival motor neuron complex and RNA polymerase II. Journal of Cell Biology 152, 75-85CrossRef Google Scholar PubMed

212Winkler, C. et al. (2005) Reduced U snRNP assembly causes motor axon degeneration in an animal model for spinal muscular atrophy. Genes and Development 19, 2320-2330CrossRef Google Scholar

213Antonellis, A. et al. (2006) Functional analyses of glycyl-tRNA synthetase mutations suggest a key role for tRNA-charging enzymes in peripheral axons. Journal of Neuroscience 26, 10397-10406CrossRef Google Scholar PubMed

214Nousiainen, H.O. et al. (2008) Mutations in mRNA export mediator GLE1 result in a fetal motoneuron disease. Nature Genetics 40, 155-157CrossRef Google Scholar

215Bolger, T.A. et al. (2008) The mRNA export factor Gle1 and inositol hexakisphosphate regulate distinct stages of translation. Cell 134, 624-633CrossRef Google Scholar PubMed

216Ou, S.H. et al. (1995) Cloning and characterization of a novel cellular protein, TDP-43, that binds to human immunodeficiency virus type 1 TAR DNA sequence motifs. Journal of Virology 69, 3584-3596CrossRef Google Scholar PubMed

217Abhyankar, M.M., Urekar, C. and Reddi, P.P. (2007) A novel CpG-free vertebrate insulator silences the testis-specific SP-10 gene in somatic tissues: role for TDP-43 in insulator function. Journal of Biological Chemistry 282, 36143-36154CrossRef Google Scholar PubMed

218Wang, X. et al. (2008) Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature 454, 126-130CrossRef Google Scholar PubMed

219Xu, Z.P. et al. (2003) Identification and characterization of an angiogenin-binding DNA sequence that stimulates luciferase reporter gene expression. Biochemistry 42, 121-128CrossRef Google Scholar PubMed

220Xu, Z.P. et al. (2002) The nuclear function of angiogenin in endothelial cells is related to rRNA production. Biochemical and Biophysical Research Communications 294, 287-292CrossRef Google Scholar PubMed

221Tsuji, T. et al. (2005) Angiogenin is translocated to the nucleus of HeLa cells and is involved in ribosomal RNA transcription and cell proliferation. Cancer Research 65, 1352-1360CrossRef Google Scholar

222Saxena, S.K. et al. (1992) Angiogenin is a cytotoxic, tRNA-specific ribonuclease in the RNase A superfamily. Journal of Biological Chemistry 267, 21982-21986CrossRef Google Scholar PubMed

Article contents

The role of RNA processing in the pathogenesis of motor neuron degeneration

Abstract

Access options

References

References

Further reading, resources and contacts

This article has been cited by the following publications. This list is generated based on data provided by Crossref.

Article contents

The role of RNA processing in the pathogenesis of motor neuron degeneration

Abstract

Access options

References

References

Further reading, resources and contacts

Save article to Kindle

Save article to Dropbox

Save article to Google Drive

Reply to: Submit a response

Your details

You have entered the maximum number of contributors

Conflicting interests