|Title:||Structural diversity and functional implications of the eukaryotic TDP gene family||Authors:||Wang, Hurng-Yi||Keywords:||TDP family;Evolution;Exon skipping;Alternative splicing||Issue Date:||2004||Publisher:||Taipei:National Taiwan University Dept Elect Engn||Start page/Pages:||130-139||Source:||Genomics||Abstract:||
TDP-43 is an RNA-binding protein that functions in mammalian cells in transcriptional repression and exon skipping. The gene encoding
TDP-43 (HGMW-approved gene symbol TARDBP) is conserved in human, mouse, Drosophila melanogaster, and Caenorhabditis elegans.
Sequence comparison of the coding regions of the TDP genes among the four taxa reveals an extraordinarily low rate of sequence divergence,
suggesting that the TDP genes carry out essential functions in these organisms. With DNA transfection assay, we have established the
importance of the glycine-rich domain for the exon-skipping activity of TDP-43. Both human and mouse TDP genes belong to a gene family
that also consists of a number of processed pseudogenes. Interestingly, combined database analysis and cDNA cloning have demonstrated
that the primary transcript of the mammalian TDP genes undergoes alternative splicing to generate 11 mRNAs, including the one encoding
TDP-43. Eight of the 11 splicing events involved the use of four each of the 5V-donor and 3V-acceptor sites, all of which reside within the last
exon of the TDP-43 mRNA. The existence of multispliced isoforms of TDP-encoded proteins provides further support for the functional
complexity of the eukaryotic TDP genes.
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