RNA degradation eliminates developmental transcripts during murine embryonic stem cell differentiation via CAPRIN1-XRN2

Juliane O. Viegas, Gajendra Kumar Azad, Yuan Lv, Lior Fishman, Tal Paltiel, Sundararaghavan Pattabiraman, Jung Eun Park, Daniel Kaganovich, Siu Kwan Sze, Michal Rabani, Miguel A. Esteban, Eran Meshorer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Embryonic stem cells (ESCs) are self-renewing and pluripotent. In recent years, factors that control pluripotency, mostly nuclear, have been identified. To identify non-nuclear regulators of ESCs, we screened an endogenously labeled fluorescent fusion-protein library in mouse ESCs. One of the more compelling hits was the cell-cycle-associated protein 1 (CAPRIN1). CAPRIN1 knockout had little effect in ESCs, but it significantly altered differentiation and gene expression programs. Using RIP-seq and SLAM-seq, we found that CAPRIN1 associates with, and promotes the degradation of, thousands of RNA transcripts. CAPRIN1 interactome identified XRN2 as the likely ribonuclease. Upon early ESC differentiation, XRN2 is located in the nucleus and colocalizes with CAPRIN1 in small RNA granules in a CAPRIN1-dependent manner. We propose that CAPRIN1 regulates an RNA degradation pathway operating during early ESC differentiation, thus eliminating undesired spuriously transcribed transcripts in ESCs.

Original languageAmerican English
Pages (from-to)2731-2744.e5
JournalDevelopmental Cell
Volume57
Issue number24
DOIs
StatePublished - 19 Dec 2022

Bibliographical note

Publisher Copyright:
© 2022 The Author(s)

Keywords

  • CAPRIN1
  • RNA degradation
  • RNA stability
  • XRN2
  • differentiation
  • embryonic stem cells
  • pluripotency
  • stress granules

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