摘要：SummaryMatrin3 (MATR3) is a nuclear RNA/DNA-binding protein that plays pleiotropic roles in gene expression regulation by directly stabilizing target RNAs and supporting the activity of transcription factors by modulating chromatin architecture. MATR3 is involved in the differentiation of neural cells, and, here, we elucidate its critical functions in regulating pluripotent circuits in human induced pluripotent stem cells (hiPSCs). MATR3 downregulation affects hiPSCs' differentiation potential by altering key pluripotency regulators' expression levels, including OCT4, NANOG, and LIN28A by pleiotropic mechanisms. MATR3 binds to theOCT4andYTHDF1promoters favoring their expression. YTHDF1, in turn, binds the m6A-modified OCT4 mRNA. Furthermore, MATR3 is recruited on ribosomes and controls pluripotency regulating the translation of specific transcripts, including NANOG and LIN28A, by direct binding and favoring their stabilization. These results show that MATR3 orchestrates the pluripotency circuitry by regulating the transcription, translational efficiency, and epitranscriptome of specific transcripts.Graphical abstractDisplay OmittedHighlights•MATR3 orchestrates the pluripotency circuitry in hiPSCs•MATR3 binds to theOCT4andYTHDF1promoters and favors their expression•YTHDF1 binds the m6A-modified OCT4 mRNA•MATR3 regulates the translation of specific transcripts including NANOG and LIN28AMolecular biology; cellular neuroscience; stem cells research
