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Context-specific regulation and function of mRNA alternative polyadenylation. | LitMetric

Context-specific regulation and function of mRNA alternative polyadenylation.

Nat Rev Mol Cell Biol

Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Published: December 2022

AI Article Synopsis

  • Alternative cleavage and polyadenylation (APA) creates different mRNA isoforms by altering the 3' untranslated regions (UTRs) of genes, and this process is influenced by cell type and environmental factors.
  • The regulation of APA involves various mechanisms, including specific RNA/DNA elements and gene regulatory pathways that impact transcription and post-transcriptional activities.
  • Recent advancements in single-cell RNA sequencing and CRISPR technology are enhancing our understanding of APA, leading to new RNA therapies that target APA processes in cancer and degenerative diseases.

Article Abstract

Alternative cleavage and polyadenylation (APA) is a widespread mechanism to generate mRNA isoforms with alternative 3' untranslated regions (UTRs). The expression of alternative 3' UTR isoforms is highly cell type specific and is further controlled in a gene-specific manner by environmental cues. In this Review, we discuss how the dynamic, fine-grained regulation of APA is accomplished by several mechanisms, including cis-regulatory elements in RNA and DNA and factors that control transcription, pre-mRNA cleavage and post-transcriptional processes. Furthermore, signalling pathways modulate the activity of these factors and integrate APA into gene regulatory programmes. Dysregulation of APA can reprogramme the outcome of signalling pathways and thus can control cellular responses to environmental changes. In addition to the regulation of protein abundance, APA has emerged as a major regulator of mRNA localization and the spatial organization of protein synthesis. This role enables the regulation of protein function through the addition of post-translational modifications or the formation of protein-protein interactions. We further discuss recent transformative advances in single-cell RNA sequencing and CRISPR-Cas technologies, which enable the mapping and functional characterization of alternative 3' UTRs in any biological context. Finally, we discuss new APA-based RNA therapeutics, including compounds that target APA in cancer and therapeutic genome editing of degenerative diseases.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9261900PMC
http://dx.doi.org/10.1038/s41580-022-00507-5DOI Listing

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