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As an RNA\u2010binding protein, Lin28a maintains some adult muscle stem cells (MuSCs) in an embryonic\u2010like state, but its RNA metabolism regulation mechanism remains unclear. BioGPS analysis revealed that Lin28a expression is significantly higher in muscle tissues than in other tissues. Lin28a\u2010positive muscle stem cells (Lin28a+ MuSCs) were sorted from <jats:italic>Lin28a\u2010CreERT2<\/jats:italic>; <jats:italic>LSL\u2010tdTomato<\/jats:italic> mouse skeletal muscle tissue, which exhibited a higher proliferation rate than the control group. Lin28a\u2010bound transcripts are enriched in various biological processes such as DNA repair, cell cycle, mitochondrial tricarboxylic acid cycle and oxidative stress response. The expression of insulin\u2010like growth factor 2 mRNA\u2010binding protein 3 (Igf2bp3) was markedly elevated in the presence of Lin28a. Co\u2010immunoprecipitation analysis further demonstrated that Lin28a associates with Igf2bp3. Immunofluorescence analyses confirmed that Lin28a, Igf2bp3 and G3bp1 colocalize to form stress granules (SG), and N6\u2010methyladenosine (m<jats:sup>6<\/jats:sup>A) modification promotes the formation of Lin28a\u2010SG. Sequencing of the transcriptome and RNAs immunoprecipitated by Lin28a, Igf2bp3 and m<jats:sup>6<\/jats:sup>A antibodies in Lin28a+ MuSCs further revealed that Lin28a and Igf2bp3 collaboratively regulate the expression of DNA repair\u2010related genes, including <jats:italic>Fancm<\/jats:italic> and <jats:italic>Usp1<\/jats:italic>. Lin28a stabilises <jats:italic>Igf2bp3<\/jats:italic>, <jats:italic>Usp1,<\/jats:italic> and <jats:italic>Fancm<\/jats:italic> mRNAs, enhancing DNA repair against oxidative or proteotoxic stress, thus promoting MuSCs self\u2010renewal. Understanding the intricate mechanisms through which Lin28a and Igf2bp3 regulate MuSCs provides a deeper understanding of stem cell self\u2010renewal, with potential implications for regenerative medicine.<\/jats:p>","DOI":"10.1111\/cpr.13707","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T05:40:47Z","timestamp":1721281247000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Lin28a forms an <scp>RNA<\/scp>\u2010binding complex with Igf2bp3 to regulate <scp>m<sup>6<\/sup>A<\/scp>\u2010modified stress response genes in stress granules of muscle stem cells"],"prefix":"10.1111","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8764-7610","authenticated-orcid":false,"given":"Dan","family":"Song","sequence":"first","affiliation":[{"name":"Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology Institute of 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