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Multilayer and MATR3-dependent regulation of mRNAs maintains pluripotency in human induced pluripotent stem cells.
Pollini, Daniele; Loffredo, Rosa; Maniscalco, Federica; Cardano, Marina; Micaelli, Mariachiara; Bonomo, Isabelle; Licata, Nausicaa Valentina; Peroni, Daniele; Tomaszewska, Weronika; Rossi, Annalisa; Crippa, Valeria; Dassi, Erik; Viero, Gabriella; Quattrone, Alessandro; Poletti, Angelo; Conti, Luciano; Provenzani, Alessandro.
Afiliação
  • Pollini D; Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.
  • Loffredo R; Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.
  • Maniscalco F; Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.
  • Cardano M; Institute of Biophysics, CNR, Trento, Italy.
  • Micaelli M; Cell Technology Core Facility, Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.
  • Bonomo I; Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.
  • Licata NV; Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.
  • Peroni D; Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.
  • Tomaszewska W; Mass Spectrometry Core Facility, Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.
  • Rossi A; Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.
  • Crippa V; Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.
  • Dassi E; Laboratorio di Biologia Applicata, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
  • Viero G; Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.
  • Quattrone A; Institute of Biophysics, CNR, Trento, Italy.
  • Poletti A; Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.
  • Conti L; Laboratorio di Biologia Applicata, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
  • Provenzani A; Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.
iScience ; 24(3): 102197, 2021 Mar 19.
Article em En | MEDLINE | ID: mdl-33733063
Matrin3 (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 the OCT4 and YTHDF1 promoters 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2021 Tipo de documento: Article