Translational control by DHX36 binding to 5′UTR G-quadruplex is essential for muscle stem-cell regenerative functions

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

2 Scopus Citations
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Author(s)

  • Xiaona Chen
  • Jie Yuan
  • Guang Xue
  • Silvia Campanario
  • Di Wang
  • Wen Wang
  • Shiau Wei Liew
  • Joan Isern
  • Yu Zhao
  • Liangqiang He
  • Yuying Li
  • Christopher J. Mann
  • Xiaohua Yu
  • Lei Wang
  • Eusebio Perdiguero
  • Wei Chen
  • Yuanchao Xue
  • Yoshikuni Nagamine
  • Hao Sun
  • Pura Muñoz-Cánoves
  • Huating Wang

Detail(s)

Original languageEnglish
Article number5043
Journal / PublicationNature Communications
Volume12
Online published19 Aug 2021
Publication statusPublished - 2021

Link(s)

Abstract

Skeletal muscle has a remarkable ability to regenerate owing to its resident stem cells (also called satellite cells, SCs). SCs are normally quiescent; when stimulated by damage, they activate and expand to form new fibers. The mechanisms underlying SC proliferative progression remain poorly understood. Here we show that DHX36, a helicase that unwinds RNA G-quadruplex (rG4) structures, is essential for muscle regeneration by regulating SC expansion. DHX36 (initially named RHAU) is barely expressed at quiescence but is highly induced during SC activation and proliferation. Inducible deletion of Dhx36 in adult SCs causes defective proliferation and muscle regeneration after damage. System-wide mapping in proliferating SCs reveals DHX36 binding predominantly to rG4 structures at various regions of mRNAs, while integrated polysome profiling shows that DHX36 promotes mRNA translation via 5′-untranslated region (UTR) rG4 binding. Furthermore, we demonstrate that DHX36 specifically regulates the translation of Gnai2 mRNA by unwinding its 5′ UTR rG4 structures and identify GNAI2 as a downstream effector of DHX36 for SC expansion. Altogether, our findings uncover DHX36 as an indispensable post-transcriptional regulator of SC function and muscle regeneration acting through binding and unwinding rG4 structures at 5′ UTR of target mRNAs.

Research Area(s)

Citation Format(s)

Translational control by DHX36 binding to 5′UTR G-quadruplex is essential for muscle stem-cell regenerative functions. / Chen, Xiaona; Yuan, Jie; Xue, Guang; Campanario, Silvia; Wang, Di; Wang, Wen; Mou, Xi; Liew, Shiau Wei; Umar, Mubarak Ishaq; Isern, Joan; Zhao, Yu; He, Liangqiang; Li, Yuying; Mann, Christopher J.; Yu, Xiaohua; Wang, Lei; Perdiguero, Eusebio; Chen, Wei; Xue, Yuanchao; Nagamine, Yoshikuni; Kwok, Chun Kit; Sun, Hao; Muñoz-Cánoves, Pura; Wang, Huating.

In: Nature Communications, Vol. 12, 5043, 2021.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review