Alternative Polyadenylation in Stem Cell Self-Renewal and Differentiation

Trends Mol Med. 2021 Jul;27(7):660-672. doi: 10.1016/j.molmed.2021.04.006. Epub 2021 May 11.

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.

Keywords: alternative polyadenylation; cell cycle; self-renewal; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 3' Untranslated Regions / genetics*
  • Animals
  • Cell Differentiation
  • Cell Self Renewal*
  • Humans
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / therapy*
  • Polyadenylation*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Regenerative Medicine*
  • Stem Cells / cytology*

Substances

  • 3' Untranslated Regions
  • RNA, Messenger