Identification of RNA-binding proteins that partner with Lin28a to regulate Dnmt3a expression

Abstract Lin28 is an evolutionary conserved RNA-binding protein that plays important roles during embryonic development and tumorigenesis. It regulates gene expression through two different post-transcriptional mechanisms. The first one is based on the regulation of miRNA biogenesis, in particular t...

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Autores principales:	Silvia Parisi, Daniela Castaldo, Silvia Piscitelli, Chiara D’Ambrosio, Giuseppina Divisato, Fabiana Passaro, Rosario Avolio, Alessia Castellucci, Paolo Gianfico, Mariorosario Masullo, Andrea Scaloni, Tommaso Russo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c56a8e72574d4abbbd06de2c3be7b365
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spelling	oai:doaj.org-article:c56a8e72574d4abbbd06de2c3be7b3652021-12-02T10:48:31ZIdentification of RNA-binding proteins that partner with Lin28a to regulate Dnmt3a expression10.1038/s41598-021-81429-82045-2322https://doaj.org/article/c56a8e72574d4abbbd06de2c3be7b3652021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81429-8https://doaj.org/toc/2045-2322Abstract Lin28 is an evolutionary conserved RNA-binding protein that plays important roles during embryonic development and tumorigenesis. It regulates gene expression through two different post-transcriptional mechanisms. The first one is based on the regulation of miRNA biogenesis, in particular that of the let-7 family, whose expression is suppressed by Lin28. Thus, loss of Lin28 leads to the upregulation of mRNAs that are targets of let-7 species. The second mechanism is based on the direct interaction of Lin28 with a large number of mRNAs, which results in the regulation of their translation. This second mechanism remains poorly understood. To address this issue, we purified high molecular weight complexes containing Lin28a in mouse embryonic stem cells (ESCs). Numerous proteins, co-purified with Lin28a, were identified by proteomic procedures and tested for their possible role in Lin28a-dependent regulation of the mRNA encoding DNA methyltransferase 3a (Dnmt3a). The results show that Lin28a activity is dependent on many proteins, including three helicases and four RNA-binding proteins. The suppression of four of these proteins, namely Ddx3x, Hnrnph1, Hnrnpu or Syncrip, interferes with the binding of Lin28a to the Dnmt3a mRNA, thus suggesting that they are part of an oligomeric ribonucleoprotein complex that is necessary for Lin28a activity.Silvia ParisiDaniela CastaldoSilvia PiscitelliChiara D’AmbrosioGiuseppina DivisatoFabiana PassaroRosario AvolioAlessia CastellucciPaolo GianficoMariorosario MasulloAndrea ScaloniTommaso RussoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Silvia Parisi Daniela Castaldo Silvia Piscitelli Chiara D’Ambrosio Giuseppina Divisato Fabiana Passaro Rosario Avolio Alessia Castellucci Paolo Gianfico Mariorosario Masullo Andrea Scaloni Tommaso Russo Identification of RNA-binding proteins that partner with Lin28a to regulate Dnmt3a expression
description	Abstract Lin28 is an evolutionary conserved RNA-binding protein that plays important roles during embryonic development and tumorigenesis. It regulates gene expression through two different post-transcriptional mechanisms. The first one is based on the regulation of miRNA biogenesis, in particular that of the let-7 family, whose expression is suppressed by Lin28. Thus, loss of Lin28 leads to the upregulation of mRNAs that are targets of let-7 species. The second mechanism is based on the direct interaction of Lin28 with a large number of mRNAs, which results in the regulation of their translation. This second mechanism remains poorly understood. To address this issue, we purified high molecular weight complexes containing Lin28a in mouse embryonic stem cells (ESCs). Numerous proteins, co-purified with Lin28a, were identified by proteomic procedures and tested for their possible role in Lin28a-dependent regulation of the mRNA encoding DNA methyltransferase 3a (Dnmt3a). The results show that Lin28a activity is dependent on many proteins, including three helicases and four RNA-binding proteins. The suppression of four of these proteins, namely Ddx3x, Hnrnph1, Hnrnpu or Syncrip, interferes with the binding of Lin28a to the Dnmt3a mRNA, thus suggesting that they are part of an oligomeric ribonucleoprotein complex that is necessary for Lin28a activity.
format	article
author	Silvia Parisi Daniela Castaldo Silvia Piscitelli Chiara D’Ambrosio Giuseppina Divisato Fabiana Passaro Rosario Avolio Alessia Castellucci Paolo Gianfico Mariorosario Masullo Andrea Scaloni Tommaso Russo
author_facet	Silvia Parisi Daniela Castaldo Silvia Piscitelli Chiara D’Ambrosio Giuseppina Divisato Fabiana Passaro Rosario Avolio Alessia Castellucci Paolo Gianfico Mariorosario Masullo Andrea Scaloni Tommaso Russo
author_sort	Silvia Parisi
title	Identification of RNA-binding proteins that partner with Lin28a to regulate Dnmt3a expression
title_short	Identification of RNA-binding proteins that partner with Lin28a to regulate Dnmt3a expression
title_full	Identification of RNA-binding proteins that partner with Lin28a to regulate Dnmt3a expression
title_fullStr	Identification of RNA-binding proteins that partner with Lin28a to regulate Dnmt3a expression
title_full_unstemmed	Identification of RNA-binding proteins that partner with Lin28a to regulate Dnmt3a expression
title_sort	identification of rna-binding proteins that partner with lin28a to regulate dnmt3a expression
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c56a8e72574d4abbbd06de2c3be7b365
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Identification of RNA-binding proteins that partner with Lin28a to regulate Dnmt3a expression

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