| First Author | Avendaño-Vázquez SE | Year | 2012 |
| Journal | Genes Dev | Volume | 26 |
| Issue | 15 | Pages | 1679-84 |
| PubMed ID | 22855830 | Mgi Jnum | J:185946 |
| Mgi Id | MGI:5430663 | Doi | 10.1101/gad.194829.112 |
| Citation | Avendano-Vazquez SE, et al. (2012) Autoregulation of TDP-43 mRNA levels involves interplay between transcription, splicing, and alternative polyA site selection. Genes Dev 26(15):1679-84 |
| abstractText | TDP-43 is a critical RNA-binding factor associated with pre-mRNA splicing in mammals. Its expression is tightly autoregulated, with loss of this regulation implicated in human neuropathology. We demonstrate that TDP-43 overexpression in humans and mice activates a 3' untranslated region (UTR) intron, resulting in excision of the proximal polyA site (PAS) pA(1). This activates a cryptic PAS that prevents TDP-43 expression through a nuclear retention mechanism. Superimposed on this process, overexpression of TDP-43 blocks recognition of pA(1) by competing with CstF-64 for PAS binding. Overall, we uncover complex interplay between transcription, splicing, and 3' end processing to effect autoregulation of TDP-43. |
