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The emerging theme of 3'UTR mRNA isoform regulation in reprogramming of cell metabolism

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BIOCHEMICAL SOCIETY TRANSACTIONS
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PORTLAND PRESS LTD
DOI: 10.1042/BST20221128

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The 3' untranslated region (3'UTR) of mRNA is crucial for post-transcriptional regulation of gene expression. Eukaryotic protein-coding genes express multiple 3'UTR isoforms due to alternative cleavage and polyadenylation (APA). Cell proliferation, differentiation, and stress conditions lead to changes in the 3'UTR isoform expression profile. This review focuses on the regulation of 3'UTR isoforms in cell metabolic reprogramming, specifically exploring cell growth and autophagy responses mediated by the mTOR pathway.
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 isoformspecific m6A modification and endomembrane association in determining differential metabolic fates of 3'UTR isoforms.

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