CFIm-mediated alternative polyadenylation safeguards the development of mammalian pre-implantation embryos

Stem Cell Reports. 2023 Jan 10;18(1):81-96. doi: 10.1016/j.stemcr.2022.11.016. Epub 2022 Dec 22.

Abstract

Alternative polyadenylation (APA) gives rise to transcripts with distinct 3' untranslated regions (3' UTRs), thereby affecting the fate of mRNAs. APA is strongly associated with cell proliferation and differentiation status, and thus likely plays a critical role in the embryo development. However, the pattern of APA in mammalian early embryos is still unknown. Here, we analyzed the 3' UTR lengths in human and mouse pre-implantation embryos using available single cell RNA-seq datasets and explored the underlying mechanism driving the changes. Although human and mouse early embryos displayed distinct patterns of 3' UTR changing, RNA metabolism pathways were involved in both species. The 3' UTR lengths are likely determined by the abundance of the cleavage factor I complex (CFIm) components NUDT21 and CPSF6 in the nucleus. Importantly, depletion of either component resulted in early embryo development arrest and 3' UTR shortening. Collectively, these data highlight an essential role for APA in the development of mammalian early embryos.

Keywords: 3′UTR length; APAtrap; CFIm; CPSF6; CPSF7; NUDT21; alternative polyadenylation; pre-implantation embryo development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cleavage And Polyadenylation Specificity Factor / genetics
  • Cleavage And Polyadenylation Specificity Factor / metabolism
  • Humans
  • Mammals* / metabolism
  • Mice
  • Polyadenylation*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • 3' Untranslated Regions
  • RNA, Messenger
  • Nudt21 protein, human
  • Cleavage And Polyadenylation Specificity Factor