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MATR3-Dependent Multilayer Regulation of OCT4, NANOG and LIN28A is Essential for the Maintenance of the Human Pluripotency

29 Pages Posted: 23 Jun 2020 Sneak Peek Status: Under Review

See all articles by Daniele Pollini

Daniele Pollini

University of Trento - Laboratory of Genomic Screening

Rosa Loffredo

University of Trento - Laboratory of Genomic Screening

Annalisa Rossi

University of Trento - Department of Cellular, Computational and Integrative Biology

Mariachiara Micaelli

University of Trento - Laboratory of Genomic Screening

Marina Cardano

University of Trento - Cell Technology Core Facility

Isabelle Bonomo

University of Trento - Laboratory of Genomic Screening

Nausicaa Valentina Licata

University of Trento - Laboratory of Genomic Screening

Daniele Peroni

University of Trento - Mass Spectrometry Core Facility

Valeria Crippa

Universita' Degli Studi Di Milano - Laboratorio di Biologia Applicata

Erik Dassi

University of Trento - Department of Cellular, Computational and Integrative Biology

Alessandro Quattrone

University of Trento - Centre for Integrative Biology (CIBIO)

Angelo Poletti

Universita' Degli Studi Di Milano - Laboratorio di Biologia Applicata

Luciano Conti

University of Trento - Laboatroy of Stem Cell Biology

Alessandro Provenzani

University of Trento - Laboratory of Genomic Screening

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Abstract

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 the expression level of key pluripotency regulators, including OCT4, NANOG, and LIN28A. MATR3 is recruited with specific initiation factors on ribosomes, and controls pluripotency regulating the translation of specific transcripts including NANOG and LIN28A by direct binding and favouring their stabilization. Moreover, MATR3 stimulates the expression of YTHDF1 , which, in turn, binds the m6A-modified OCT4 mRNA. These results show that MATR3 orchestrates the pluripotency circuitry by modulating the translational efficiency and regulating the epitranscriptome of specific transcripts.

Keywords: MATR3, hiPSCs, N6-methyladenosine (m6A), OCT4, NANOG, LIN28A, YTHDF1, translational efficiency, pluripotency circuits, polysomes, epitranscriptome

Suggested Citation

Pollini, Daniele and Loffredo, Rosa and Rossi, Annalisa and Micaelli, Mariachiara and Cardano, Marina and Bonomo, Isabelle and Licata, Nausicaa Valentina and Peroni, Daniele and Crippa, Valeria and Dassi, Erik and Quattrone, Alessandro and Poletti, Angelo and Conti, Luciano and Provenzani, Alessandro, MATR3-Dependent Multilayer Regulation of OCT4, NANOG and LIN28A is Essential for the Maintenance of the Human Pluripotency. Available at SSRN: https://ssrn.com/abstract=3614119 or http://dx.doi.org/10.2139/ssrn.3614119
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Daniele Pollini

University of Trento - Laboratory of Genomic Screening ( email )

Via Giuseppe Verdi 26
Trento, Trento 38152
Italy

Rosa Loffredo

University of Trento - Laboratory of Genomic Screening ( email )

Via Giuseppe Verdi 26
Trento, Trento 38152
Italy

Annalisa Rossi

University of Trento - Department of Cellular, Computational and Integrative Biology ( email )

Italy

Mariachiara Micaelli

University of Trento - Laboratory of Genomic Screening ( email )

Via Giuseppe Verdi 26
Trento, Trento 38152
Italy

Marina Cardano

University of Trento - Cell Technology Core Facility ( email )

Via Giuseppe Verdi 26
Trento, Trento 38152
Italy

Isabelle Bonomo

University of Trento - Laboratory of Genomic Screening ( email )

Via Giuseppe Verdi 26
Trento, Trento 38152
Italy

Nausicaa Valentina Licata

University of Trento - Laboratory of Genomic Screening ( email )

Via Giuseppe Verdi 26
Trento, Trento 38152
Italy

Daniele Peroni

University of Trento - Mass Spectrometry Core Facility ( email )

Via Giuseppe Verdi 26
Trento, Trento 38152
Italy

Valeria Crippa

Universita' Degli Studi Di Milano - Laboratorio di Biologia Applicata ( email )

VIA FESTA DEL PERDONO 7
MILAN, 20122
Italy

Erik Dassi

University of Trento - Department of Cellular, Computational and Integrative Biology ( email )

Italy

Alessandro Quattrone

University of Trento - Centre for Integrative Biology (CIBIO)

via Sommarive n. 9, Povo (TN)
Povo, Trentino 38123
Italy

Angelo Poletti

Universita' Degli Studi Di Milano - Laboratorio di Biologia Applicata ( email )

VIA FESTA DEL PERDONO 7
MILAN, 20122
Italy

Luciano Conti

University of Trento - Laboatroy of Stem Cell Biology ( email )

Via Giuseppe Verdi 26
Trento, Trento 38152
Italy

Alessandro Provenzani (Contact Author)

University of Trento - Laboratory of Genomic Screening ( email )

Via Giuseppe Verdi 26
Trento, Trento 38152
Italy

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