Alternative Polyadenylation in Stem Cell Self-Renewal and Differentiation. Issue 7 (July 2021)

• Record Type: Journal Article
• Authors: Sommerkamp, Pia; Cabezas-Wallscheid, Nina; Trumpp, Andreas
• Is Part Of: Trends in molecular medicine. Volume 27:Issue 7(2021)
• Page Start: 660
• Page End: 672
• Publication Date: 2021-07
• Subjects: stem cells -- alternative polyadenylation -- self-renewal -- cell cycle; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; Physiology, Pathological -- Periodicals; 572.8
• DOI: 10.1016/j.molmed.2021.04.006
• Languages: English
• ISSNs: 1471-4914

Abstract

Abstract : Cellular function is shaped by transcriptional and post-transcriptional mechanisms, including alternative polyadenylation (APA). By directly controlling 3′- untranslated region (UTR) length and the selection of the last exon, APA regulates up to 70% of all cellular transcripts influencing RNA stability, output, and protein isoform expression. Cell-state-dependent 3′-UTR shortening has been identified as a hallmark of cellular proliferation. Hence, quiescent/dormant stem cells are characterized by long 3′-UTRs, whereas proliferative stem/progenitor cells exhibit 3′-UTR shortening. Here, the latest studies analyzing the role of APA in regulating stem cell state, self-renewal, differentiation, and metabolism are reviewed. The new role of APA in controlling stem cell fate opens novel potential therapeutic avenues in the field of regenerative medicine. Highlights: Alternative polyadenylation (APA) controls the cellular 3′- untranslated region (UTR) landscape influencing RNA stability, output, protein localization, and protein isoform expression. Novel sequencing and analysis approaches allow the characterization of APA profiles in rare cell subsets, including stem cells. These analyses reveal APA to be differentially regulated in stem cell and progenitor compartments as well as in embryonic compared with adult stem cells. Overall, proliferative stem cells exhibit globally shortened 3′-UTRs, while lengthened 3′-UTR patterns are observed in quiescent/dormant stem cell compartments. A literature-based novel model suggests that APA controls stem cell self-renewal, potency, and fate by simultaneously regulating mRNA stability, protein output, and metabolic activity at the global level.