Human TAP and Saccharomyces cerevisiae
Mex67p belong to a family of proteins that mediate mRNA
export. Computer searches identified previously two Caenorhabditis
elegans genes, C15H11.3 and C15H11.6, that encode
putative homologs of hTAP and Mex67p (Segref et al., EMBO
J, 1997, 16:3256–3271). Using RNA interference
experiments in C. elegans, we found that functional
knockout of C15H11.3 resulted in nuclear accumulation of
poly(A)-containing RNAs and was lethal for both embryos
and adult nematodes. No embryonic or progeny abnormality
was observed in functional knockout of C15H11.6. Taken
together, these data established that the C15H11.3 gene
product is an ortholog of hTAP and Mex67p; thus, it was
named Ce-NXF-1. Ce-NXF-1 binds RNA directly and is a nucleocytoplasmic
shuttle protein accumulating in the nucleoplasm and at
the nuclear rim. The rim association is mediated via unique
signals present in the C-terminal portion of all TAP/NXF
and Mex67p proteins. This region was shown to interact
with the FG-repeat domains of nucleoporins Nup98, Nup153,
and Nup214, indicating that the rim association occurs
through components of the nuclear pore complex. In summary,
Ce-NXF-1 belongs together with hTAP and Mex67p to a family
of proteins that participate in mRNA export and can provide
a direct molecular link between mRNAs and components of
the nuclear pore complex. Therefore, despite differences
in mRNA metabolism between these species, they utilize
a conserved mRNA transport mechanism.