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

Embryonic stem cells (ESCs) are self-renewing and pluripotent. In recent years, factors that control pluripo-tency, 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 signif-icantly 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 inter-actome identified XRN2 as the likely ribonuclease. Upon early ESC differentiation, XRN2 is located in the nu-cleus 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 elim-inating undesired spuriously transcribed transcripts in ESCs.

Automated summary

CAPRIN1 is a factor that regulates an RNA degradation pathway in embryonic stem cells, and it has significant effects on early differentiation and gene expression programs.