Downregulation of CFIm25 amplifies dermal fibrosis through alternative polyadenylation.

ABSTRACT: Systemic sclerosis (SSc; scleroderma) is a multisystem fibrotic disease. The mammalian cleavage factor I 25-kD subunit (CFIm25; encoded by NUDT21) is a key regulator of alternative polyadenylation, and its depletion causes predominantly 3'UTR shortening through loss of stimulation of distal polyadenylation sites. A shortened 3'UTR will often lack microRNA target sites, resulting in increased mRNA translation due to evasion of microRNA-mediated repression. Herein, we report that CFlm25 is downregulated in SSc skin, primary dermal fibroblasts, and two murine models of dermal fibrosis. Knockdown of CFIm25 in normal skin fibroblasts is sufficient to promote the 3'UTR shortening of key TGFβ-regulated fibrotic genes and enhance their protein expression. Moreover, several of these fibrotic transc

SUBMITTER: Weng T 

PROVIDER: S-EPMC7041714 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature