The 3′ untranslated region (3′UTR) of mRNA plays a key role in the post-transcriptional regulation of gene expression. Most eukaryotic protein-coding genes express 3′UTR isoforms owing to alternative cleavage and polyadenylation (APA). The 3′UTR isoform expression profile of a cell changes in cell proliferation, differentiation, and stress conditions. Here, we review the emerging theme of regulation of 3′UTR isoforms in cell metabolic reprogramming, focusing on cell growth and autophagy responses through the mTOR pathway. We discuss regulatory events that converge on the Cleavage Factor I complex, a master regulator of APA in 3′UTRs, and recent understandings of isoform-specific m6A modification and endomembrane association in determining differential metabolic fates of 3′UTR isoforms.

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