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PRMT1-mediated methylation of the microprocessor-associated proteins regulates microRNA biogenesis
MicroRNA (miRNA) biogenesis is a tightly controlled multi-step process operated in the nucleus by the activity of the Microprocessor and its associated proteins. Through high resolution mass spectrometry (MS)- proteomics we discovered that this complex is extensively methylated, with 84 methylated s...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943135/ https://www.ncbi.nlm.nih.gov/pubmed/31777917 http://dx.doi.org/10.1093/nar/gkz1051 |
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author | Spadotto, Valeria Giambruno, Roberto Massignani, Enrico Mihailovich, Marija Maniaci, Marianna Patuzzo, Francesca Ghini, Francesco Nicassio, Francesco Bonaldi, Tiziana |
author_facet | Spadotto, Valeria Giambruno, Roberto Massignani, Enrico Mihailovich, Marija Maniaci, Marianna Patuzzo, Francesca Ghini, Francesco Nicassio, Francesco Bonaldi, Tiziana |
author_sort | Spadotto, Valeria |
collection | PubMed |
description | MicroRNA (miRNA) biogenesis is a tightly controlled multi-step process operated in the nucleus by the activity of the Microprocessor and its associated proteins. Through high resolution mass spectrometry (MS)- proteomics we discovered that this complex is extensively methylated, with 84 methylated sites associated to 19 out of its 24 subunits. The majority of the modifications occurs on arginine (R) residues (61), leading to 81 methylation events, while 30 lysine (K)-methylation events occurs on 23 sites of the complex. Interestingly, both depletion and pharmacological inhibition of the Type-I Protein Arginine Methyltransferases (PRMTs) lead to a widespread change in the methylation state of the complex and induce global decrease of miRNA expression, as a consequence of the impairment of the pri-to-pre-miRNA processing step. In particular, we show that the reduced methylation of the Microprocessor subunit ILF3 is linked to its diminished binding to the pri-miRNAs miR-15a/16, miR-17–92, miR-301a and miR-331. Our study uncovers a previously uncharacterized role of R-methylation in the regulation of miRNA biogenesis in mammalian cells. |
format | Online Article Text |
id | pubmed-6943135 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-69431352020-01-08 PRMT1-mediated methylation of the microprocessor-associated proteins regulates microRNA biogenesis Spadotto, Valeria Giambruno, Roberto Massignani, Enrico Mihailovich, Marija Maniaci, Marianna Patuzzo, Francesca Ghini, Francesco Nicassio, Francesco Bonaldi, Tiziana Nucleic Acids Res Data Resources and Analyses MicroRNA (miRNA) biogenesis is a tightly controlled multi-step process operated in the nucleus by the activity of the Microprocessor and its associated proteins. Through high resolution mass spectrometry (MS)- proteomics we discovered that this complex is extensively methylated, with 84 methylated sites associated to 19 out of its 24 subunits. The majority of the modifications occurs on arginine (R) residues (61), leading to 81 methylation events, while 30 lysine (K)-methylation events occurs on 23 sites of the complex. Interestingly, both depletion and pharmacological inhibition of the Type-I Protein Arginine Methyltransferases (PRMTs) lead to a widespread change in the methylation state of the complex and induce global decrease of miRNA expression, as a consequence of the impairment of the pri-to-pre-miRNA processing step. In particular, we show that the reduced methylation of the Microprocessor subunit ILF3 is linked to its diminished binding to the pri-miRNAs miR-15a/16, miR-17–92, miR-301a and miR-331. Our study uncovers a previously uncharacterized role of R-methylation in the regulation of miRNA biogenesis in mammalian cells. Oxford University Press 2020-01-10 2019-11-28 /pmc/articles/PMC6943135/ /pubmed/31777917 http://dx.doi.org/10.1093/nar/gkz1051 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Data Resources and Analyses Spadotto, Valeria Giambruno, Roberto Massignani, Enrico Mihailovich, Marija Maniaci, Marianna Patuzzo, Francesca Ghini, Francesco Nicassio, Francesco Bonaldi, Tiziana PRMT1-mediated methylation of the microprocessor-associated proteins regulates microRNA biogenesis |
title | PRMT1-mediated methylation of the microprocessor-associated proteins regulates microRNA biogenesis |
title_full | PRMT1-mediated methylation of the microprocessor-associated proteins regulates microRNA biogenesis |
title_fullStr | PRMT1-mediated methylation of the microprocessor-associated proteins regulates microRNA biogenesis |
title_full_unstemmed | PRMT1-mediated methylation of the microprocessor-associated proteins regulates microRNA biogenesis |
title_short | PRMT1-mediated methylation of the microprocessor-associated proteins regulates microRNA biogenesis |
title_sort | prmt1-mediated methylation of the microprocessor-associated proteins regulates microrna biogenesis |
topic | Data Resources and Analyses |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943135/ https://www.ncbi.nlm.nih.gov/pubmed/31777917 http://dx.doi.org/10.1093/nar/gkz1051 |
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