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Control of Gene Expression by RNA Binding Protein Action on Alternative Translation Initiation Sites

Transcript levels do not faithfully predict protein levels, due to post-transcriptional regulation of gene expression mediated by RNA binding proteins (RBPs) and non-coding RNAs. We developed a multivariate linear regression model integrating RBP levels and predicted RBP-mRNA regulatory interactions...

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Detalles Bibliográficos
Autores principales: Re, Angela, Waldron, Levi, Quattrone, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5140048/
https://www.ncbi.nlm.nih.gov/pubmed/27923063
http://dx.doi.org/10.1371/journal.pcbi.1005198
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author Re, Angela
Waldron, Levi
Quattrone, Alessandro
author_facet Re, Angela
Waldron, Levi
Quattrone, Alessandro
author_sort Re, Angela
collection PubMed
description Transcript levels do not faithfully predict protein levels, due to post-transcriptional regulation of gene expression mediated by RNA binding proteins (RBPs) and non-coding RNAs. We developed a multivariate linear regression model integrating RBP levels and predicted RBP-mRNA regulatory interactions from matched transcript and protein datasets. RBPs significantly improved the accuracy in predicting protein abundance of a portion of the total modeled mRNAs in three panels of tissues and cells and for different methods employed in the detection of mRNA and protein. The presence of upstream translation initiation sites (uTISs) at the mRNA 5’ untranslated regions was strongly associated with improvement in predictive accuracy. On the basis of these observations, we propose that the recently discovered widespread uTISs in the human genome can be a previously unappreciated substrate of translational control mediated by RBPs.
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spelling pubmed-51400482016-12-21 Control of Gene Expression by RNA Binding Protein Action on Alternative Translation Initiation Sites Re, Angela Waldron, Levi Quattrone, Alessandro PLoS Comput Biol Research Article Transcript levels do not faithfully predict protein levels, due to post-transcriptional regulation of gene expression mediated by RNA binding proteins (RBPs) and non-coding RNAs. We developed a multivariate linear regression model integrating RBP levels and predicted RBP-mRNA regulatory interactions from matched transcript and protein datasets. RBPs significantly improved the accuracy in predicting protein abundance of a portion of the total modeled mRNAs in three panels of tissues and cells and for different methods employed in the detection of mRNA and protein. The presence of upstream translation initiation sites (uTISs) at the mRNA 5’ untranslated regions was strongly associated with improvement in predictive accuracy. On the basis of these observations, we propose that the recently discovered widespread uTISs in the human genome can be a previously unappreciated substrate of translational control mediated by RBPs. Public Library of Science 2016-12-06 /pmc/articles/PMC5140048/ /pubmed/27923063 http://dx.doi.org/10.1371/journal.pcbi.1005198 Text en © 2016 Re et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Re, Angela
Waldron, Levi
Quattrone, Alessandro
Control of Gene Expression by RNA Binding Protein Action on Alternative Translation Initiation Sites
title Control of Gene Expression by RNA Binding Protein Action on Alternative Translation Initiation Sites
title_full Control of Gene Expression by RNA Binding Protein Action on Alternative Translation Initiation Sites
title_fullStr Control of Gene Expression by RNA Binding Protein Action on Alternative Translation Initiation Sites
title_full_unstemmed Control of Gene Expression by RNA Binding Protein Action on Alternative Translation Initiation Sites
title_short Control of Gene Expression by RNA Binding Protein Action on Alternative Translation Initiation Sites
title_sort control of gene expression by rna binding protein action on alternative translation initiation sites
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5140048/
https://www.ncbi.nlm.nih.gov/pubmed/27923063
http://dx.doi.org/10.1371/journal.pcbi.1005198
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