Abstract:
: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.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Avendaño-Vázquez SE,Dhir A,Bembich S,Buratti E,Proudfoot N,Baralle FEdoi
10.1101/gad.194829.112subject
Has Abstractpub_date
2012-08-01 00:00:00pages
1679-84issue
15eissn
0890-9369issn
1549-5477pii
26/15/1679journal_volume
26pub_type
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