CPEB1 directs muscle stem cell activation by reprogramming the translational landscape

Wenshu Zeng, Lu Yue, Kim S. W. Lam, Wenxin Zhang, Wai-Kin So, Erin H. Y. Tse and Tom H. Cheung ()
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Wenshu Zeng: The Hong Kong University of Science and Technology
Lu Yue: The Hong Kong University of Science and Technology
Kim S. W. Lam: The Hong Kong University of Science and Technology
Wenxin Zhang: The Hong Kong University of Science and Technology
Wai-Kin So: The Hong Kong University of Science and Technology
Erin H. Y. Tse: The Hong Kong University of Science and Technology
Tom H. Cheung: The Hong Kong University of Science and Technology

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract Skeletal muscle stem cells, also called Satellite Cells (SCs), are actively maintained in quiescence but can activate quickly upon extrinsic stimuli. However, the mechanisms of how quiescent SCs (QSCs) activate swiftly remain elusive. Here, using a whole mouse perfusion fixation approach to obtain bona fide QSCs, we identify massive proteomic changes during the quiescence-to-activation transition in pathways such as chromatin maintenance, metabolism, transcription, and translation. Discordant correlation of transcriptomic and proteomic changes reveals potential translational regulation upon SC activation. Importantly, we show Cytoplasmic Polyadenylation Element Binding protein 1 (CPEB1), post-transcriptionally affects protein translation during SC activation by binding to the 3′ UTRs of different transcripts. We demonstrate phosphorylation-dependent CPEB1 promoted Myod1 protein synthesis by binding to the cytoplasmic polyadenylation elements (CPEs) within its 3′ UTRs to regulate SC activation and muscle regeneration. Our study characterizes CPEB1 as a key regulator to reprogram the translational landscape directing SC activation and subsequent proliferation.

Date: 2022
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DOI: 10.1038/s41467-022-28612-1

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