CPEB1 directs muscle stem cell activation by reprogramming the translational landscape

• Published in: Nature communications Vol. 13; no. 1; p. 947
• Main Authors: Zeng, Wenshu, Yue, Lu, Lam, Kim S. W., Zhang, Wenxin, So, Wai-Kin, Tse, Erin H. Y., Cheung, Tom H.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.02.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/100; 13/106; 13/109; 13/31; 13/89; 14/1; 14/19; 14/34; 3' Untranslated Regions - genetics; 45; 45/100; 45/90; 45/91; 631/337/1645; 631/337/475; 631/532/2439; 631/532/2443; Animals; Cell activation; Cell Line; Cell proliferation; Cells, Cultured; Chromatin; Disease Models, Animal; Gene Expression Regulation; HEK293 Cells; Humanities and Social Sciences; Humans; Male; Metabolism; Mice; Mice, Transgenic; mRNA Cleavage and Polyadenylation Factors - metabolism; multidisciplinary; Muscle, Skeletal - cytology; Muscle, Skeletal - injuries; Muscles; Musculoskeletal system; MyoD Protein - biosynthesis; Perfusion; Phosphorylation; Polyadenylation; Post-transcription; Protein biosynthesis; Protein Biosynthesis - genetics; Protein synthesis; Proteins; Proteomics; Regeneration; Regeneration - genetics; RNA-Seq; Satellite cells; Satellite Cells, Skeletal Muscle - physiology; Science; Science (multidisciplinary); Skeletal muscle; Stem cell transplantation; Stem cells; Transcription Factors - metabolism; Transcriptomics; Translation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-28612-1

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. Skeletal muscle stem cells are actively maintained in quiescence, but can activate quickly upon extrinsic stimulation. Here the authors show that CPEB1 promotes muscle stem cell activation by reprogramming the translational landscape.