Nuclear TARBP2 Drives Oncogenic Dysregulation of RNA Splicing and Decay.

ABSTRACT: Post-transcriptional regulation of RNA stability is a key step in gene expression control. We describe a regulatory program, mediated by the RNA binding protein TARBP2, that controls RNA stability in the nucleus. TARBP2 binding to pre-mRNAs results in increased intron retention, subsequently leading to targeted degradation of TARBP2-bound transcripts. This is mediated by TARBP2 recruitment of the m⁶A RNA methylation machinery to its target transcripts, where deposition of m⁶A marks influences the recruitment of splicing regulators, inhibiting efficient splicing. Interactions between TARBP2 and the nucleoprotein TPR then promote degradation of these TARBP2-bound transcripts by the nuclear exosome. Additionally, analysis of clinical gene expression datasets revealed a f

SUBMITTER: Fish L 

PROVIDER: S-EPMC6731133 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature