MicroRNAs: A small contribution from worms

doi:10.1017/CBO9780511546402.007

4 - MicroRNAs: A small contribution from worms

Published online by Cambridge University Press: 31 July 2009

Amy E. Pasquinelli

Edited by

Krishnarao Appasani

Foreword by

Andrew Fire and

Marshall Nirenberg

Show author details

Amy E. Pasquinelli: Affiliation:
Molecular Biology Section, University of California
Krishnarao Appasani: Affiliation:
GeneExpression Systems, Inc., Massachusetts
Andrew Fire: Affiliation:
Stanford University, California

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Summary

Introduction

The 2002 Nobel Prize for Medicine was awarded to Sydney Brenner, Robert Horvitz and John Sulston for their seminal work in establishing the nematode Caenorhabditis elegans as a model genetic organism for studying development and behavior. One of the most sensational discoveries to emerge from C. elegans is the identification of tiny, non-coding RNA genes that regulate development. The original report of a 22 nucleotide (nt) RNA essential for controlling temporal patterning in the worm was unprecedented. Seven years passed before another 22-nt RNA gene was found, once again through genetic studies of developmental timing in C. elegans. This second tiny RNA gene turned out not to be a worm oddity, but instead it was shown to be expressed in most animal species. Thus, the general existence of 22-nt RNA genes was established and the hunt for additional RNAs of this type intensified. Hundreds of ∼22-nt RNA genes have now been uncovered in plants and animals. It is not a coincidence that the tiny size of these endogenous RNAs, called microRNAs (miRNAs), is similar to that of the small interfering RNAs (siRNAs) that direct RNA interference (RNAi); common cellular factors and mechanisms participate in the expression and function of these ∼22-nt RNAs. This chapter focuses on how the discovery of 22-nt RNA genes in C. elegans revealed the broad existence of miRNAs and how the regulation of gene expression by miRNAs compares to RNAi.

Type: Chapter
Information: RNA Interference Technology
From Basic Science to Drug Development
, pp. 69 - 83

DOI: https://doi.org/10.1017/CBO9780511546402.007 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2005

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References

Abrahante, J. E., Daul, A. L., Li, M., Volk, M. L., Tennessen, J. M., Miller, E. A. and Rougvie, A. E. (2003). The Caenorhabditis elegans hunchback-like gene lin-57/hbl-1 controls developmental time and is regulated by microRNAs. Developmental Cell, 4, 625–637CrossRef Google Scholar PubMed

Ambros, V. and Horvitz, H. R. (1984). Heterochronic mutants of the nematode Caenorhabditis elegans. Science, 226, 409–416CrossRef Google Scholar PubMed

Ambros, V. and Horvitz, H. R. (1987). The lin-14 locus of Caenorhabditis elegans controls the time of expression of specific postembryonic developmental events. Genes & Development, 1, 398–414CrossRef Google Scholar PubMed

Ambros, V. (1989). A hierarchy of regulatory genes controls a larva-to-adult developmental switch in C. elegans. Cell, 57, 49–57CrossRef Google Scholar PubMed

Ambros, V. (2001). microRNAs: Tiny regulators with great potential. Cell, 107, 823–826CrossRef Google Scholar PubMed

Ambros, V. (2003). microRNA pathways in flies and worms: Growth, death, fat, stress, and timing. Cell, 113, 673–676CrossRef Google Scholar

Ambros, V., Bartel, B., Bartel, D. P., Burge, C. B., Carrington, J. C., Chen, X., Dreyfuss, G., Eddy, S. R., Griffiths-Jones, S., Marshall, M., Matzke, M., Ruvkun, G. and Tuschl, T. (2003a). A uniform system for microRNA annotation. RNA, 9, 277–279CrossRef Google Scholar

Ambros, V., Lee, R. C., Lavanway, A., Williams, P. T. and Jewell, D. (2003b). microRNAs and other tiny endogenous RNAs in C. elegans. Current Biology, 13, 807–818CrossRef Google Scholar

Banerjee, D. and Slack, F. (2002). Control of developmental timing by small temporal RNAs: A paradigm for RNA-mediated regulation of gene expression. Bioessays, 24, 119–129CrossRef Google Scholar PubMed

Bashirullah, A., Pasquinelli, A. E., Kiger, A. A., Perrimon, N., Ruvkun, G. and Thummel, C. S. (2003). Coordinate regulation of small temporal RNAs at the onset of Drosophila metamorphosis. Developmental Biology, 259, 1–8CrossRef Google Scholar PubMed

Bernstein, E., Caudy, A. A., Hammond, S. M. and Hannon, G. J. (2001). Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature, 409, 363–366CrossRef Google Scholar PubMed

Bohmert, K., Camus, I., Bellini, C., Bouchez, D., Caboche, M. and Benning, C. (1998). AGO1 defines a novel locus of Arabidopsis controlling leaf development. European Molecular Biology Organization Journal, 17, 170–180CrossRef Google Scholar PubMed

Caplen, N. J., Fleenor, J., Fire, A. and Morgan, R. A. (2000). dsRNA-mediated gene silencing in cultured Drosophila cells: A tissue culture model for the analysis of RNA interference. Gene, 252, 95–105CrossRef Google Scholar PubMed

Carthew, R. W. (2001). Gene silencing by double-stranded RNA. Current Opinions in Cell Biology, 13, 244–248CrossRef Google Scholar PubMed

Cerutti, L., Mian, N. and Bateman, A. (2000). Domains in gene silencing and cell differentiation proteins: The novel PAZ domain and redefinition of the Piwi domain. Trends in Biochemical Sciences, 25, 481–482CrossRef Google Scholar PubMed

Chalfie, M., Horvitz, H. R. and Sulston, J. E. (1981). Mutations that lead to reiterations in the cell lineages of C. elegans. Cell, 24, 59–69CrossRef Google Scholar PubMed

Dennis, C. (2002). The brave new world of RNA. Nature, 418, 122–124CrossRef Google Scholar PubMed

Doench, J. G., Petersen, C. P. and Sharp, P. A. (2003). siRNAs can function as miRNAs. Genes & Development, 17, 438–442CrossRef Google Scholar PubMed

Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K. and Tuschl, T. (2001a). Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature, 411, 494–498CrossRef Google Scholar

Elbashir, S. M., Lendeckel, W. and Tuschl, T. (2001b). RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes & Development, 15, 188–200CrossRef Google Scholar

Elbashir, S. M., Martinez, J., Patkaniowska, A., Lendeckel, W. and Tuschl, T. (2001c). Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. European Molecular Biology Organization Journal, 20, 6877–6888CrossRef Google Scholar

Fagard, M., Boutet, S., Morel, J. B., Bellini, C. and Vaucheret, H. (2000). AGO1, QDE-2, and RDE-1 are related proteins required for post-transcriptional gene silencing in plants, quelling in fungi, and RNA interference in animals. Proceedings of the National Academy of Sciences USA, 97, 11650–11654CrossRef Google Scholar PubMed

Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E. and Mello, C. C. (1998). Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature, 391, 806–811CrossRef Google Scholar PubMed

Grad, Y., Aach, J., Hayes, G. D., Reinhart, B. J., Church, G. M., Ruvkun, G. and Kim, J. (2003). Computational and experimental identification of C. elegans microRNAs. Molecular Cell, 11, 1253–1263CrossRef Google Scholar PubMed

Grishok, A., Pasquinelli, A. E., Conte, D., Li, N., Parrish, S., Ha, I., Baillie, D. L., Fire, A., Ruvkun, G. and Mello, C. C. (2001). Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell, 106, 23–34CrossRef Google Scholar PubMed

Grosshans, H. and Slack, F. J. (2002). Micro-RNAs: Small is plentiful. Journal of Cell Biology, 156, 17–21CrossRef Google Scholar

Ha, I., Wightman, B. and Ruvkun, G. (1996). A bulged lin-4/lin-14 RNA duplex is sufficient for Caenorhabditis elegans lin-14 temporal gradient formation. Genes & Development, 10, 3041–3050CrossRef Google Scholar PubMed

Hamilton, A. J. and Baulcombe, D. C. (1999). A species of small antisense RNA in posttranscriptional gene silencing in plants. Science, 286, 950–952CrossRef Google Scholar PubMed

Hammond, S. M., Bernstein, E., Beach, D. and Hannon, G. J. (2000). An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature, 404, 293–296CrossRef Google Scholar PubMed

Hunter, C. and Poethig, R. S. (2003). miSSING LINKS: miRNAs and plant development. Current Opinion in Genetics and Development, 13, 372–378CrossRef Google Scholar PubMed

Hüttenhofer, A., Brosius, J., Bachellerie, J.-P. (2003). RNomics: identification and function of small, non-messenger RNAs. Current Opinion in Chemical Biology, 6, 835–843CrossRef Google Scholar

Hütvagner, G., McLachlan, J., Pasquinelli, A. E., Balint, E., Tuschl, T. and Zamore, P. D. (2001). A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science, 293, 834–838CrossRef Google Scholar PubMed

Hütvagner, G. and Zamore, P. D. (2002). A microRNA in a multiple-turnover RNAi enzyme complex. Science, 297, 2056–2060CrossRef Google Scholar

Johnson, S. M., Lin, S. Y. and Slack, F. J. (2003). The time of appearance of the C. elegans let-7 microRNA is transcriptionally controlled utilizing a temporal regulatory element in its promoter. Developmental Biology, 259, 364–379CrossRef Google Scholar

Ketting, R. F., Fischer, S. E., Bernstein, E., Sijen, T., Hannon, G. J. and Plasterk, R. H. (2001). Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes & Development, 15, 2654–2659CrossRef Google Scholar PubMed

Knight, S. W. and Bass, B. L. (2001). A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans. Science, 293, 2269–2271CrossRef Google Scholar PubMed

Lagos-Quintana, M., Rauhut, R., Lendeckel, W. and Tuschl, T. (2001). Identification of novel genes coding for small expressed RNAs. Science, 294, 853–858CrossRef Google Scholar PubMed

Lagos-Quintana, M., Rauhut, R., Yalcin, A., Meyer, J., Lendeckel, W. and Tuschl, T. (2002). Identification of tissue-specific microRNAs from mouse. Current Biology, 12, 735–739CrossRef Google Scholar PubMed

Lai, E. C. and Posakony, J. W. (1997). The Bearded box, a novel 3′ UTR sequence motif, mediates negative post-transcriptional regulation of Bearded and Enhancer of split Complex gene expression. Development, 124, 4847–4856Google Scholar PubMed

Lai, E. C., Burks, C. and Posakony, J. W. (1998). The K box, a conserved 3′ UTR sequence motif, negatively regulates accumulation of enhancer of split complex transcripts. Development, 125, 4077–4088Google Scholar

Lai, E. C. (2002). Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation. Nature Genetics, 30, 363–364CrossRef Google Scholar PubMed

Lai, E. C., Tomancak, P., Williams, R. W. and Rubin, G. M. (2003). Computational identification of Drosophila microRNA genes. Genome Biology, 4, R42CrossRef Google Scholar PubMed

Lau, N. C., Lim, E. P., Weinstein, E. G. and Bartel, D. P. (2001). An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science, 294, 858–862CrossRef Google Scholar PubMed

Lee, R. C. and Ambros, V. (2001). An extensive class of small RNAs in Caenorhabditis elegans. Science, 294, 862–864CrossRef Google Scholar PubMed

Lee, R. C., Feinbaum, R. L. and Ambros, V. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell, 75, 843–854CrossRef Google Scholar

Lee, Y., Jeon, K., Lee, J. T., Kim, S. and Kim, V. N. (2002). microRNA maturation: stepwise processing and subcellular localization. European Molecular Biology Organization Journal, 21, 4663–4670CrossRef Google Scholar PubMed

Lim, L. P., Glasner, M. E., Yekta, S., Burge, C. B. and Bartel, D. P. (2003a). Vertebrate microRNA genes. Science, 299, 1540CrossRef Google Scholar

Lim, L. P., Lau, N. C., Weinstein, E. G., Abdelhakim, A., Yekta, S., Rhoades, M. W., Burge, C. B. and Bartel, D. P. (2003b). The microRNAs of Caenorhabditis elegans. Genes & Development, 17, 991–1008CrossRef Google Scholar

Lin, S. Y., Johnson, S. M., Abraham, M., Vella, M. C., Pasquinelli, A., Gamberi, C., Gottlieb, E. and Slack, F. J. (2003). The C. elegans hunchback homolog, hbl-1, controls temporal patterning and is a probable microRNA target. Developmental Cell, 4, 639–650CrossRef Google Scholar

Llave, C., Xie, Z., Kasschau, K. D. and Carrington, J. C. (2002). Cleavage of Scarecrow-like mRNA targets directed by a class of Arabidopsis miRNA. Science, 297, 2053–2056CrossRef Google Scholar PubMed

McManus, M. T., Petersen, C. P., Haines, B. B., Chen, J. and Sharp, P. A. (2002). Gene silencing using micro-RNA designed hairpins. RNA, 8, 842–850CrossRef Google Scholar PubMed

Moss, E. G., Lee, R. C. and Ambros, V. (1997). The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA. Cell, 88, 637–646CrossRef Google Scholar

Moss, E. G. and Poethig, R. S. (2002). microRNAs: Something new under the sun. Current Biology, 12, R688–690CrossRef Google Scholar PubMed

Moss, E. G. and Tang, L. (2003). Conservation of the heterochronic regulator Lin-28, its developmental expression and microRNA complementary sites. Developmental Biology, 258, 432–442CrossRef Google Scholar PubMed

Mourelatos, Z., Dostie, J., Paushkin, S., Sharma, A., Charroux, B., Abel, L., Rappsilber, J., Mann, M. and Dreyfuss, G. (2002). miRNPs A novel class of ribonucleoproteins containing numerous microRNAs. Genes & Development, 16, 720–728CrossRef Google Scholar PubMed

Olsen, P. H. and Ambros, V. (1999). The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Developmental Biology, 216, 671–680CrossRef Google Scholar PubMed

Park, W., Li, J., Song, R., Messing, J. and Chen, X. (2002). CARPEL FACTORY, a Dicer homolog, and HEN1, a novel protein, act in microRNA metabolism in Arabidopsis thaliana. Current Biology, 12, 1484–1495CrossRef Google Scholar PubMed

Parrish, S., Fleenor, J., Xu, S., Mello, C. and Fire, A. (2000). Functional anatomy of a dsRNA trigger. Differential requirement for the two trigger strands in RNA interference. Molecular Cell, 6, 1077–1087CrossRef Google Scholar PubMed

Pasquinelli, A. E., Reinhart, B. J., Slack, F., Martindale, M. Q., Kuroda, M. I., Maller, B., Hayward, D. C., Ball, E. E., Degnan, B., Muller, P., Spring, J., Srinivasan, A., Fishman, M., Finnerty, J., Corbo, J., Levine, M., Leahy, P., Davidson, E. and Ruvkun, G. (2000). Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature, 408, 86–89Google Scholar PubMed

Pasquinelli, A. E. (2002). microRNAs: Deviants no longer. Trends in Genetics, 18, 171–173CrossRef Google Scholar PubMed

Pasquinelli, A. E. and Ruvkun, G. (2002). Control of developmental timing by microRNAs and their targets. Annual Reviews of Cell and Developmental Biology, 18, 495–513CrossRef Google Scholar PubMed

Pasquinelli, A. E., McCoy, A., Jimenez, E., Salo, E., Ruvkun, G., Martindale, M. Q. and Baguna, J. (2003). Expression of the 22 nucleotide let-7 heterochronic RNA throughout the Metazoa: A role in life history evolution?Evolution & Development, 5, 372–378CrossRef Google Scholar PubMed

Reinhart, B. J., Slack, F. J., Basson, M., Pasquinelli, A. E., Bettinger, J. C., Rougvie, A. E., Horvitz, H. R. and Ruvkun, G. (2000). The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature, 403, 901–906CrossRef Google Scholar PubMed

Reinhart, B. J., Weinstein, E. G., Rhoades, M. W., Bartel, B. and Bartel, D. P. (2002). microRNAs in plants. Genes & Development, 16, 1616–1626CrossRef Google Scholar PubMed

Ruvkun, G. and Giusto, J. (1989). The Caenorhabditis elegans heterochronic gene lin-14 encodes a nuclear protein that forms a temporal developmental switch. Nature, 338, 313–319CrossRef Google Scholar PubMed

Ruvkun, G. (2001). Molecular biology. Glimpses of a tiny RNA world. Science, 294, 797–799CrossRef Google Scholar PubMed

Schwarz, D. S. and Zamore, P. D. (2002). Why do miRNAs live in the miRNP?Genes & Development, 16, 1025–1031CrossRef Google Scholar PubMed

Seggerson, K., Tang, L. and Moss, E. G. (2002). Two genetic circuits repress the Caenorhabditis elegans heterochronic gene lin-28 after translation initiation. Developmental Biology, 243, 215–225CrossRef Google Scholar PubMed

Sempere, L. F., Sokol, N. S., Dubrovsky, E. B., Berger, E. M. and Ambros, V. (2003). Temporal regulation of microRNA expression in Drosophila melanogaster mediated by hormonal signals and broad-Complex gene activity. Developmental Biology, 259, 9–18CrossRef Google Scholar PubMed

Slack, F. J. and Ruvkun, G. (1998). A novel repeat domain that is often associated with RING finger and B- box motifs. Trends Biochem Sci, 23, 474–475CrossRef Google Scholar PubMed

Slack, F. J., Basson, M., Liu, Z., Ambros, V., Horvitz, H. R. and Ruvkun, G. (2000). The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor. Molecular Cell, 5, 659–669CrossRef Google Scholar

Sulston, J. E. and Horvitz, H. R. (1977). Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Developmental Biology, 56, 110–156CrossRef Google Scholar PubMed

Sulston, J. E. and Horvitz, H. R. (1981). Abnormal cell lineages in mutants of the nematode Caenorhabditis elegans. Developmental Biology, 82, 41–55CrossRef Google Scholar PubMed

Tabara, H., Sarkissian, M., Kelly, W. G., Fleenor, J., Grishok, A., Timmons, L., Fire, A. and Mello, C. C. (1999). The rde-1 gene, RNA interference, and transposon silencing in C. elegans. Cell, 99, 123–132CrossRef Google Scholar PubMed

Tuschl, T., Zamore, P. D., Lehmann, R., Bartel, D. P. and Sharp, P. A. (1999). Targeted mRNA degradation by double-stranded RNA in vitro. Genes & Development, 13, 3191–3197CrossRef Google Scholar PubMed

Wightman, B., Ha, I. and Ruvkun, G. (1993). Posttranscriptional regulation of the heterochronic gene lin-14 by lin- 4 mediates temporal pattern formation in C. elegans. Cell, 75, 855–862CrossRef Google Scholar PubMed

Yang, D., Lu, H. and Erickson, J. W. (2000). Evidence that processed small dsRNAs may mediate sequence-specific mRNA degradation during RNAi in Drosophila embryos. Current Biology, 10, 1191–1200CrossRef Google Scholar PubMed

Zamore, P. D., Tuschl, T., Sharp, P. A. and Bartel, D. P. (2000). RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell, 101, 25–33CrossRef Google Scholar PubMed

Zamore, P. D. (2002). Ancient pathways programmed by small RNAs. Science, 296, 1265–1269CrossRef Google Scholar PubMed

Zeng, Y., Wagner, E. J. and Cullen, B. R. (2002). Both natural and designed micro RNAs can inhibit the expression of cognate mRNAs when expressed in human cells. Molecular Cell, 9, 1327–1333CrossRef Google Scholar PubMed

Zeng, Y., Yi, R. and Cullen, B. R. (2003). microRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proceedings of the National Academy of Sciences U S A, 100, 9779–9784CrossRef Google Scholar PubMed