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Inferring microRNA regulation: A proteome perspective

Post-transcriptional regulation in multicellular organisms is mediated by microRNAs. However, the principles that determine if a gene is regulated by miRNAs are poorly understood. Previous works focused mostly on miRNA seed matches and other features of the 3′-UTR of transcripts. These common approa...

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Autores principales: Ofer, Dan, Linial, Michal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9493312/
https://www.ncbi.nlm.nih.gov/pubmed/36158574
http://dx.doi.org/10.3389/fmolb.2022.916639
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author Ofer, Dan
Linial, Michal
author_facet Ofer, Dan
Linial, Michal
author_sort Ofer, Dan
collection PubMed
description Post-transcriptional regulation in multicellular organisms is mediated by microRNAs. However, the principles that determine if a gene is regulated by miRNAs are poorly understood. Previous works focused mostly on miRNA seed matches and other features of the 3′-UTR of transcripts. These common approaches rely on knowledge of the miRNA families, and computational approaches still yield poor, inconsistent results, with many false positives. In this work, we present a different paradigm for predicting miRNA-regulated genes based on the encoded proteins. In a novel, automated machine learning framework, we use sequence as well as diverse functional annotations to train models on multiple organisms using experimentally validated data. We present insights from tens of millions of features extracted and ranked from different modalities. We show high predictive performance per organism and in generalization across species. We provide a list of novel predictions including Danio rerio (zebrafish) and Arabidopsis thaliana (mouse-ear cress). We compare genomic models and observe that our protein model outperforms, whereas a unified model improves on both. While most membranous and disease related proteins are regulated by miRNAs, the G-protein coupled receptor (GPCR) family is an exception, being mostly unregulated by miRNAs. We further show that the evolutionary conservation among paralogs does not imply any coherence in miRNA regulation. We conclude that duplicated paralogous genes that often changed their function, also diverse in their tendency to be miRNA regulated. We conclude that protein function is informative across species in predicting post-transcriptional miRNA regulation in living cells.
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spelling pubmed-94933122022-09-23 Inferring microRNA regulation: A proteome perspective Ofer, Dan Linial, Michal Front Mol Biosci Molecular Biosciences Post-transcriptional regulation in multicellular organisms is mediated by microRNAs. However, the principles that determine if a gene is regulated by miRNAs are poorly understood. Previous works focused mostly on miRNA seed matches and other features of the 3′-UTR of transcripts. These common approaches rely on knowledge of the miRNA families, and computational approaches still yield poor, inconsistent results, with many false positives. In this work, we present a different paradigm for predicting miRNA-regulated genes based on the encoded proteins. In a novel, automated machine learning framework, we use sequence as well as diverse functional annotations to train models on multiple organisms using experimentally validated data. We present insights from tens of millions of features extracted and ranked from different modalities. We show high predictive performance per organism and in generalization across species. We provide a list of novel predictions including Danio rerio (zebrafish) and Arabidopsis thaliana (mouse-ear cress). We compare genomic models and observe that our protein model outperforms, whereas a unified model improves on both. While most membranous and disease related proteins are regulated by miRNAs, the G-protein coupled receptor (GPCR) family is an exception, being mostly unregulated by miRNAs. We further show that the evolutionary conservation among paralogs does not imply any coherence in miRNA regulation. We conclude that duplicated paralogous genes that often changed their function, also diverse in their tendency to be miRNA regulated. We conclude that protein function is informative across species in predicting post-transcriptional miRNA regulation in living cells. Frontiers Media S.A. 2022-09-08 /pmc/articles/PMC9493312/ /pubmed/36158574 http://dx.doi.org/10.3389/fmolb.2022.916639 Text en Copyright © 2022 Ofer and Linial. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Ofer, Dan
Linial, Michal
Inferring microRNA regulation: A proteome perspective
title Inferring microRNA regulation: A proteome perspective
title_full Inferring microRNA regulation: A proteome perspective
title_fullStr Inferring microRNA regulation: A proteome perspective
title_full_unstemmed Inferring microRNA regulation: A proteome perspective
title_short Inferring microRNA regulation: A proteome perspective
title_sort inferring microrna regulation: a proteome perspective
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9493312/
https://www.ncbi.nlm.nih.gov/pubmed/36158574
http://dx.doi.org/10.3389/fmolb.2022.916639
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