Structural diversity and functional implications of the eukaryotic TDP gene family.
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 5'-donor and 3'-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.
Wang
Hurng-Yi
HY
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, Republic of China.
Wang
I-Fan
IF
Bose
Jayaramakrishnan
J
Shen
C-K James
CK
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics; D002460:Cell Line; D017124:Conserved Sequence / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D004331:Drosophila melanogaster / Q000235:genetics; D005057:Eukaryotic Cells / Q000378:metabolism*; D019143:Evolution, Molecular; D005796:Genes / Q000235:genetics; D014644:Genetic Variation; D005998:Glycine / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D005998:Glycine