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The comprehensive interactomes of human adenosine RNA methyltransferases and demethylases reveal distinct functional and regulatory features

N6-methyladenosine (m(6)A) and N6,2′-O-dimethyladenosine (m(6)Am) are two abundant modifications found in mRNAs and ncRNAs that can regulate multiple aspects of RNA biology. They function mainly by regulating interactions with specific RNA-binding proteins. Both modifications are linked to developme...

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Autores principales: Covelo-Molares, Helena, Obrdlik, Ales, Poštulková, Ivana, Dohnálková, Michaela, Gregorová, Pavlína, Ganji, Ranjani, Potěšil, David, Gawriyski, Lisa, Varjosalo, Markku, Vaňáčová, Štěpánka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8565353/
https://www.ncbi.nlm.nih.gov/pubmed/34634806
http://dx.doi.org/10.1093/nar/gkab900
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author Covelo-Molares, Helena
Obrdlik, Ales
Poštulková, Ivana
Dohnálková, Michaela
Gregorová, Pavlína
Ganji, Ranjani
Potěšil, David
Gawriyski, Lisa
Varjosalo, Markku
Vaňáčová, Štěpánka
author_facet Covelo-Molares, Helena
Obrdlik, Ales
Poštulková, Ivana
Dohnálková, Michaela
Gregorová, Pavlína
Ganji, Ranjani
Potěšil, David
Gawriyski, Lisa
Varjosalo, Markku
Vaňáčová, Štěpánka
author_sort Covelo-Molares, Helena
collection PubMed
description N6-methyladenosine (m(6)A) and N6,2′-O-dimethyladenosine (m(6)Am) are two abundant modifications found in mRNAs and ncRNAs that can regulate multiple aspects of RNA biology. They function mainly by regulating interactions with specific RNA-binding proteins. Both modifications are linked to development, disease and stress response. To date, three methyltransferases and two demethylases have been identified that modify adenosines in mammalian mRNAs. Here, we present a comprehensive analysis of the interactomes of these enzymes. PCIF1 protein network comprises mostly factors involved in nascent RNA synthesis by RNA polymerase II, whereas ALKBH5 is closely linked with most aspects of pre-mRNA processing and mRNA export to the cytoplasm. METTL16 resides in subcellular compartments co-inhabited by several other RNA modifiers and processing factors. FTO interactome positions this demethylase at a crossroad between RNA transcription, RNA processing and DNA replication and repair. Altogether, these enzymes share limited spatial interactomes, pointing to specific molecular mechanisms of their regulation.
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spelling pubmed-85653532021-11-04 The comprehensive interactomes of human adenosine RNA methyltransferases and demethylases reveal distinct functional and regulatory features Covelo-Molares, Helena Obrdlik, Ales Poštulková, Ivana Dohnálková, Michaela Gregorová, Pavlína Ganji, Ranjani Potěšil, David Gawriyski, Lisa Varjosalo, Markku Vaňáčová, Štěpánka Nucleic Acids Res Data Resources and Analyses N6-methyladenosine (m(6)A) and N6,2′-O-dimethyladenosine (m(6)Am) are two abundant modifications found in mRNAs and ncRNAs that can regulate multiple aspects of RNA biology. They function mainly by regulating interactions with specific RNA-binding proteins. Both modifications are linked to development, disease and stress response. To date, three methyltransferases and two demethylases have been identified that modify adenosines in mammalian mRNAs. Here, we present a comprehensive analysis of the interactomes of these enzymes. PCIF1 protein network comprises mostly factors involved in nascent RNA synthesis by RNA polymerase II, whereas ALKBH5 is closely linked with most aspects of pre-mRNA processing and mRNA export to the cytoplasm. METTL16 resides in subcellular compartments co-inhabited by several other RNA modifiers and processing factors. FTO interactome positions this demethylase at a crossroad between RNA transcription, RNA processing and DNA replication and repair. Altogether, these enzymes share limited spatial interactomes, pointing to specific molecular mechanisms of their regulation. Oxford University Press 2021-10-11 /pmc/articles/PMC8565353/ /pubmed/34634806 http://dx.doi.org/10.1093/nar/gkab900 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Data Resources and Analyses
Covelo-Molares, Helena
Obrdlik, Ales
Poštulková, Ivana
Dohnálková, Michaela
Gregorová, Pavlína
Ganji, Ranjani
Potěšil, David
Gawriyski, Lisa
Varjosalo, Markku
Vaňáčová, Štěpánka
The comprehensive interactomes of human adenosine RNA methyltransferases and demethylases reveal distinct functional and regulatory features
title The comprehensive interactomes of human adenosine RNA methyltransferases and demethylases reveal distinct functional and regulatory features
title_full The comprehensive interactomes of human adenosine RNA methyltransferases and demethylases reveal distinct functional and regulatory features
title_fullStr The comprehensive interactomes of human adenosine RNA methyltransferases and demethylases reveal distinct functional and regulatory features
title_full_unstemmed The comprehensive interactomes of human adenosine RNA methyltransferases and demethylases reveal distinct functional and regulatory features
title_short The comprehensive interactomes of human adenosine RNA methyltransferases and demethylases reveal distinct functional and regulatory features
title_sort comprehensive interactomes of human adenosine rna methyltransferases and demethylases reveal distinct functional and regulatory features
topic Data Resources and Analyses
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8565353/
https://www.ncbi.nlm.nih.gov/pubmed/34634806
http://dx.doi.org/10.1093/nar/gkab900
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