A twin UGUA motif directs the balance between gene isoforms through CFIm and the mTORC1 signaling pathway.

ABSTRACT: Alternative polyadenylation (APA) generates mRNA isoforms and diversifies gene expression. Here we report the discovery that the mTORC1 signaling pathway balances the expression of two Trim9/TRIM9 isoforms through APA regulation in human and mouse. We showed that CFIm components, CPSF6 and NUDT21, promote the short Trim9/TRIM9 isoform (Trim9-S/TRIM9-S) expression. In addition, we identified an evolutionarily conserved twin UGUA motif, UGUAYUGUA, in TRIM9-S polyadenylation site (PAS) that is critical for its regulation by CPSF6. We found additional CPSF6-regulated PASs with similar twin UGUA motifs in human and experimentally validated the twin UGUA motif functionality in BMPR1B, MOB4, and BRD4-L. Importantly, we showed that inserting a twin

SUBMITTER: Herron RS 

PROVIDER: S-EPMC10476966 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature