RNA helicase DDX10 is Required for Pluripotency of Stem Cells by Regulating 18S rRNA Processing (CLIP-Seq)

Ribosomes, as a protein synthesis machine, are required for stem cells to maintain self-renewal. Here, we find that DEAD-box RNA helicase DDX10 is necessary for cellular pluripotency acquisition in somatic cell reprogramming, and in mouse embryonic stem cells (mESCs), DDX10 degradation disrupts cellular homeostasis, leads to cell cycle arrest in G1 phase and markedly inhibits cell proliferation. DDX10 is localized in dense fiber component (DFC) and granular component (GC), mainly binds to 45S ribosomal RNA (rRNA) and participates in regulating ribosome biogenesis. Specifically, DDX10 degradation prevents the release of U3 snoRNA from pre-rRNA, and disrupts pre-rRNA processing and maturation of 18S rRNA, leading to impaired ribosomal small subunit production. Together, this study reveals that DDX10 functions as an important regulator of ribosome biogenesis, and is essential for the survival, induction and maintenance of pluripotent stem cells. Overall design: CLIP-seq experiments were performed in mESCs with stable expression of Flag-tagged DDX10.