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Tytuł pozycji:

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

Tytuł:
Translational control by DHX36 binding to 5'UTR G-quadruplex is essential for muscle stem-cell regenerative functions.
Autorzy:
Chen X; Department of Orthopaedics and Traumatology, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong SAR, China.
Yuan J; Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong SAR, China.
Xue G; Department of Orthopaedics and Traumatology, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong SAR, China.
Campanario S; Department of Experimental & Health Sciences, Universitat Pompeu Fabra (UPF), CIBERNED, ICREA, Barcelona, Spain.; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Wang D; Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.; University of Chinese Academy of Sciences, Beijing, China.
Wang W; Department of Biology, Southern University of Science and Technology, Shenzhen, China.
Mou X; Department of Chemistry and State Key Laboratory of Marine Pollution, City University of Hong Kong, Kowloon Tong, Hong Kong SAR, China.
Liew SW; Department of Chemistry and State Key Laboratory of Marine Pollution, City University of Hong Kong, Kowloon Tong, Hong Kong SAR, China.
Umar MI; Department of Chemistry and State Key Laboratory of Marine Pollution, City University of Hong Kong, Kowloon Tong, Hong Kong SAR, China.
Isern J; Department of Experimental & Health Sciences, Universitat Pompeu Fabra (UPF), CIBERNED, ICREA, Barcelona, Spain.; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Zhao Y; Department of Orthopaedics and Traumatology, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong SAR, China.
He L; Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong SAR, China.
Li Y; Department of Orthopaedics and Traumatology, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong SAR, China.
Mann CJ; Department of Experimental & Health Sciences, Universitat Pompeu Fabra (UPF), CIBERNED, ICREA, Barcelona, Spain.
Yu X; Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Wang L; Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.; College of Life Sciences, Xinyang Normal University, Xinyang, China.
Perdiguero E; Department of Experimental & Health Sciences, Universitat Pompeu Fabra (UPF), CIBERNED, ICREA, Barcelona, Spain.
Chen W; Department of Biology, Southern University of Science and Technology, Shenzhen, China.
Xue Y; Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.; University of Chinese Academy of Sciences, Beijing, China.
Nagamine Y; Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Basel, Switzerland.
Kwok CK; Department of Chemistry and State Key Laboratory of Marine Pollution, City University of Hong Kong, Kowloon Tong, Hong Kong SAR, China.; Shenzhen Research Institute of City University of Hong Kong, Shenzhen, China.
Sun H; Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong SAR, China. .
Muñoz-Cánoves P; Department of Experimental & Health Sciences, Universitat Pompeu Fabra (UPF), CIBERNED, ICREA, Barcelona, Spain. .; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. .
Wang H; Department of Orthopaedics and Traumatology, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong SAR, China. .
Źródło:
Nature communications [Nat Commun] 2021 Aug 19; Vol. 12 (1), pp. 5043. Date of Electronic Publication: 2021 Aug 19.
Typ publikacji:
Journal Article; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Original Publication: [London] : Nature Pub. Group
MeSH Terms:
5' Untranslated Regions*
G-Quadruplexes*
DEAD-box RNA Helicases/*metabolism
Muscles/*cytology
Regeneration/*physiology
Stem Cells/*cytology
Animals ; Animals, Genetically Modified ; Cells, Cultured ; Disease Models, Animal ; GTP-Binding Protein alpha Subunit, Gi2/metabolism ; Gene Expression Regulation ; Humans ; Mice ; Muscles/metabolism ; Myoblasts/metabolism ; Polyribosomes/metabolism ; Protein Biosynthesis ; RNA, Messenger/genetics ; Stem Cells/metabolism
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Substance Nomenclature:
0 (5' Untranslated Regions)
0 (RNA, Messenger)
EC 3.6.1.- (Dhx36 protein, mouse)
EC 3.6.4.13 (DEAD-box RNA Helicases)
EC 3.6.5.1 (GTP-Binding Protein alpha Subunit, Gi2)
EC 3.6.5.1 (Gnai2 protein, mouse)
Entry Date(s):
Date Created: 20210820 Date Completed: 20210916 Latest Revision: 20210923
Update Code:
20240104
PubMed Central ID:
PMC8377060
DOI:
10.1038/s41467-021-25170-w
PMID:
34413292
Czasopismo naukowe
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.
(© 2021. The Author(s).)

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