Studies of alternative isoforms provide insight into TDP-43 autoregulation and pathogenesis.

ABSTRACT: TDP-43 is a soluble, nuclear protein that undergoes cytoplasmic redistribution and aggregation in the majority of cases of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. TDP-43 autoregulates the abundance of its own transcript TARDBP by binding to an intron in the 3' untranslated region, although the mechanisms underlying this activity have been debated. Herein, we provide the most extensive analysis of TARDBP transcript yet undertaken. We detail the existence of a plethora of complex splicing events and alternative poly(A) use and provide data that explain the discrepancies reported to date regarding the autoregulatory capacity of TDP-43. Additionally, although many splice isoforms emanating from the TARDBP locus contain the regulated intron in the 3' UTR, we find on

SUBMITTER: D'Alton S 

PROVIDER: S-EPMC4509932 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature