Lockd promotes myoblast proliferation and muscle regeneration via binding with DHX36 to facilitate 5' UTR rG4 unwinding and Anp32e translation

Xiaona Chen; Guang Xue; Jieyu Zhao; Yuwei Zhang; Suyang Zhang; Wen Wang; Yang Li; Jie Yuan; Liangqiang He; Chun Yin Chan; Yan Liu; Wei  Chen; Yu Zhao; Ping Hu; Hao  Sun; Chun Kit Kwok; Huating Wang

doi:10.1016/j.celrep.2022.110927

Lockd promotes myoblast proliferation and muscle regeneration via binding with DHX36 to facilitate 5' UTR rG4 unwinding and Anp32e translation

Xiaona Chen, Guang Xue, Jieyu Zhao, Yuwei Zhang, Suyang Zhang, Wen Wang, Yang Li, Jie Yuan, Liangqiang He, Chun Yin Chan, Yan Liu, Wei Chen, Yu Zhao, Ping Hu, Hao Sun^*, Chun Kit Kwok^*, Huating Wang^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

19 Citations (Scopus)

61 Downloads (CityUHK Scholars)

Abstract

Adult muscle stem cells, also known as satellite cells (SCs), play pivotal roles in muscle regeneration, and long non-coding RNA (lncRNA) functions in SCs remain largely unknown. Here, we identify a lncRNA, Lockd, which is induced in activated SCs upon acute muscle injury. We demonstrate that Lockd promotes SC proliferation; deletion of Lockd leads to cell-cycle arrest, and in vivo repression of Lockd in mouse muscles hinders regeneration process. Mechanistically, we show that Lockd directly interacts with RNA helicase DHX36 and the 5′end of Lockd possesses the strongest binding with DHX36. Furthermore, we demonstrate that Lockd stabilizes the interaction between DHX36 and EIF3B proteins; synergistically, this complex unwinds the RNA G-quadruplex (rG4) structure formed at Anp32e mRNA 5′ UTR and promotes the translation of ANP32E protein, which is required for myoblast proliferation. Altogether, our findings identify a regulatory Lockd/DHX36/Anp32e axis that promotes myoblast proliferation and acute-injury-induced muscle regeneration.

Original language	English
Article number	110907
Journal	Cell Reports
Volume	39
Issue number	10
Online published	7 Jun 2022
DOIs	https://doi.org/10.1016/j.celrep.2022.110927
Publication status	Published - 7 Jun 2022

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Keywords

ANP32E
CP: Molecular biology
CP: Stem cell research
DHX36
EIF3B
Lockd
muscle regeneration
post-transcriptional regulation
RNA G-quadruplexes
satellite cells
translational regulation

Publisher's Copyright Statement

This full text is made available under CC-BY-NC-ND 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/

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10.1016/j.celrep.2022.110927

104794477.pdfFinal Published version, 6.61 MBLicence: CC BY-NC-ND

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Chen, X., Xue, G., Zhao, J., Zhang, Y., Zhang, S., Wang, W., Li, Y., Yuan, J., He, L., Chan, C. Y., Liu, Y., Chen, W., Zhao, Y., Hu, P., Sun, H., Kwok, C. K., & Wang, H. (2022). Lockd promotes myoblast proliferation and muscle regeneration via binding with DHX36 to facilitate 5' UTR rG4 unwinding and Anp32e translation. Cell Reports, 39(10), Article 110907. https://doi.org/10.1016/j.celrep.2022.110927

@article{6f86f90998224b26bd76ac872ed5e5dc,

title = "Lockd promotes myoblast proliferation and muscle regeneration via binding with DHX36 to facilitate 5' UTR rG4 unwinding and Anp32e translation",

abstract = "Adult muscle stem cells, also known as satellite cells (SCs), play pivotal roles in muscle regeneration, and long non-coding RNA (lncRNA) functions in SCs remain largely unknown. Here, we identify a lncRNA, Lockd, which is induced in activated SCs upon acute muscle injury. We demonstrate that Lockd promotes SC proliferation; deletion of Lockd leads to cell-cycle arrest, and in vivo repression of Lockd in mouse muscles hinders regeneration process. Mechanistically, we show that Lockd directly interacts with RNA helicase DHX36 and the 5′end of Lockd possesses the strongest binding with DHX36. Furthermore, we demonstrate that Lockd stabilizes the interaction between DHX36 and EIF3B proteins; synergistically, this complex unwinds the RNA G-quadruplex (rG4) structure formed at Anp32e mRNA 5′ UTR and promotes the translation of ANP32E protein, which is required for myoblast proliferation. Altogether, our findings identify a regulatory Lockd/DHX36/Anp32e axis that promotes myoblast proliferation and acute-injury-induced muscle regeneration.",

keywords = "ANP32E, CP: Molecular biology, CP: Stem cell research, DHX36, EIF3B, Lockd, muscle regeneration, post-transcriptional regulation, RNA G-quadruplexes, satellite cells, translational regulation",

author = "Xiaona Chen and Guang Xue and Jieyu Zhao and Yuwei Zhang and Suyang Zhang and Wen Wang and Yang Li and Jie Yuan and Liangqiang He and Chan, {Chun Yin} and Yan Liu and Wei Chen and Yu Zhao and Ping Hu and Hao Sun and Kwok, {Chun Kit} and Huating Wang",

year = "2022",

month = jun,

day = "7",

doi = "10.1016/j.celrep.2022.110927",

language = "English",

volume = "39",

journal = "Cell Reports",

issn = "2639-1856",

publisher = "Elsevier B.V.",

number = "10",

}

Chen, X, Xue, G, Zhao, J, Zhang, Y, Zhang, S, Wang, W, Li, Y, Yuan, J, He, L, Chan, CY, Liu, Y, Chen, W, Zhao, Y, Hu, P, Sun, H, Kwok, CK & Wang, H 2022, 'Lockd promotes myoblast proliferation and muscle regeneration via binding with DHX36 to facilitate 5' UTR rG4 unwinding and Anp32e translation', Cell Reports, vol. 39, no. 10, 110907. https://doi.org/10.1016/j.celrep.2022.110927

TY - JOUR

T1 - Lockd promotes myoblast proliferation and muscle regeneration via binding with DHX36 to facilitate 5' UTR rG4 unwinding and Anp32e translation

AU - Chen, Xiaona

AU - Xue, Guang

AU - Zhao, Jieyu

AU - Zhang, Yuwei

AU - Zhang, Suyang

AU - Wang, Wen

AU - Li, Yang

AU - Yuan, Jie

AU - He, Liangqiang

AU - Chan, Chun Yin

AU - Liu, Yan

AU - Chen, Wei

AU - Zhao, Yu

AU - Hu, Ping

AU - Sun, Hao

AU - Kwok, Chun Kit

AU - Wang, Huating

PY - 2022/6/7

Y1 - 2022/6/7

N2 - Adult muscle stem cells, also known as satellite cells (SCs), play pivotal roles in muscle regeneration, and long non-coding RNA (lncRNA) functions in SCs remain largely unknown. Here, we identify a lncRNA, Lockd, which is induced in activated SCs upon acute muscle injury. We demonstrate that Lockd promotes SC proliferation; deletion of Lockd leads to cell-cycle arrest, and in vivo repression of Lockd in mouse muscles hinders regeneration process. Mechanistically, we show that Lockd directly interacts with RNA helicase DHX36 and the 5′end of Lockd possesses the strongest binding with DHX36. Furthermore, we demonstrate that Lockd stabilizes the interaction between DHX36 and EIF3B proteins; synergistically, this complex unwinds the RNA G-quadruplex (rG4) structure formed at Anp32e mRNA 5′ UTR and promotes the translation of ANP32E protein, which is required for myoblast proliferation. Altogether, our findings identify a regulatory Lockd/DHX36/Anp32e axis that promotes myoblast proliferation and acute-injury-induced muscle regeneration.

AB - Adult muscle stem cells, also known as satellite cells (SCs), play pivotal roles in muscle regeneration, and long non-coding RNA (lncRNA) functions in SCs remain largely unknown. Here, we identify a lncRNA, Lockd, which is induced in activated SCs upon acute muscle injury. We demonstrate that Lockd promotes SC proliferation; deletion of Lockd leads to cell-cycle arrest, and in vivo repression of Lockd in mouse muscles hinders regeneration process. Mechanistically, we show that Lockd directly interacts with RNA helicase DHX36 and the 5′end of Lockd possesses the strongest binding with DHX36. Furthermore, we demonstrate that Lockd stabilizes the interaction between DHX36 and EIF3B proteins; synergistically, this complex unwinds the RNA G-quadruplex (rG4) structure formed at Anp32e mRNA 5′ UTR and promotes the translation of ANP32E protein, which is required for myoblast proliferation. Altogether, our findings identify a regulatory Lockd/DHX36/Anp32e axis that promotes myoblast proliferation and acute-injury-induced muscle regeneration.

KW - ANP32E

KW - CP: Molecular biology

KW - CP: Stem cell research

KW - DHX36

KW - EIF3B

KW - Lockd

KW - muscle regeneration

KW - post-transcriptional regulation

KW - RNA G-quadruplexes

KW - satellite cells

KW - translational regulation

UR - http://www.scopus.com/inward/record.url?scp=85131626286&partnerID=8YFLogxK

UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85131626286&origin=recordpage

U2 - 10.1016/j.celrep.2022.110927

DO - 10.1016/j.celrep.2022.110927

M3 - RGC 21 - Publication in refereed journal

C2 - 35675771

SN - 2639-1856

VL - 39

JO - Cell Reports

JF - Cell Reports

IS - 10

M1 - 110907

ER -

Lockd promotes myoblast proliferation and muscle regeneration via binding with DHX36 to facilitate 5' UTR rG4 unwinding and Anp32e translation

Abstract

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Research Keywords

Publisher's Copyright Statement

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CROU_RMG: Deciphering Long Non-coding RNA Structures, Interactions, and their Functions in Skeletal Myogenic Differentiation-RMGS

GRF: Developing Novel L-RNA Aptamer to Inhibit Telomerase Activity and Regulate G-Quadruplex-Mediated Gene Expression

GRF: Mapping and Targeting of RNA G-quadruplex Structures in the Human Non-coding Transcriptome

Cite this

Lockd promotes myoblast proliferation and muscle regeneration via binding with DHX36 to facilitate 5' UTR rG4 unwinding and Anp32e translation

Abstract

UN SDGs

Research Keywords

Publisher's Copyright Statement

Access Output

Other Access Options

Permanent Link

Other Files and Links

Fingerprint

Projects

CROU_RMG: Deciphering Long Non-coding RNA Structures, Interactions, and their Functions in Skeletal Myogenic Differentiation-RMGS

GRF: Developing Novel L-RNA Aptamer to Inhibit Telomerase Activity and Regulate G-Quadruplex-Mediated Gene Expression

GRF: Mapping and Targeting of RNA G-quadruplex Structures in the Human Non-coding Transcriptome

Cite this