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Transcription Impacts the Efficiency of mRNA Translation via Co-transcriptional N6-adenosine Methylation

Transcription and translation are two main pillars of gene expression. Due to the different timings, spots of action, and mechanisms of regulation, these processes are mainly regarded as distinct and generally uncoupled, despite serving a common purpose. Here, we sought for a possible connection bet...

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Autores principales: Slobodin, Boris, Han, Ruiqi, Calderone, Vittorio, Vrielink, Joachim A.F. Oude, Loayza-Puch, Fabricio, Elkon, Ran, Agami, Reuven
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388891/
https://www.ncbi.nlm.nih.gov/pubmed/28388414
http://dx.doi.org/10.1016/j.cell.2017.03.031
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author Slobodin, Boris
Han, Ruiqi
Calderone, Vittorio
Vrielink, Joachim A.F. Oude
Loayza-Puch, Fabricio
Elkon, Ran
Agami, Reuven
author_facet Slobodin, Boris
Han, Ruiqi
Calderone, Vittorio
Vrielink, Joachim A.F. Oude
Loayza-Puch, Fabricio
Elkon, Ran
Agami, Reuven
author_sort Slobodin, Boris
collection PubMed
description Transcription and translation are two main pillars of gene expression. Due to the different timings, spots of action, and mechanisms of regulation, these processes are mainly regarded as distinct and generally uncoupled, despite serving a common purpose. Here, we sought for a possible connection between transcription and translation. Employing an unbiased screen of multiple human promoters, we identified a positive effect of TATA box on translation and a general coupling between mRNA expression and translational efficiency. Using a CRISPR-Cas9-mediated approach, genome-wide analyses, and in vitro experiments, we show that the rate of transcription regulates the efficiency of translation. Furthermore, we demonstrate that m(6)A modification of mRNAs is co-transcriptional and depends upon the dynamics of the transcribing RNAPII. Suboptimal transcription rates lead to elevated m(6)A content, which may result in reduced translation. This study uncovers a general and widespread link between transcription and translation that is governed by epigenetic modification of mRNAs.
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spelling pubmed-53888912017-04-17 Transcription Impacts the Efficiency of mRNA Translation via Co-transcriptional N6-adenosine Methylation Slobodin, Boris Han, Ruiqi Calderone, Vittorio Vrielink, Joachim A.F. Oude Loayza-Puch, Fabricio Elkon, Ran Agami, Reuven Cell Article Transcription and translation are two main pillars of gene expression. Due to the different timings, spots of action, and mechanisms of regulation, these processes are mainly regarded as distinct and generally uncoupled, despite serving a common purpose. Here, we sought for a possible connection between transcription and translation. Employing an unbiased screen of multiple human promoters, we identified a positive effect of TATA box on translation and a general coupling between mRNA expression and translational efficiency. Using a CRISPR-Cas9-mediated approach, genome-wide analyses, and in vitro experiments, we show that the rate of transcription regulates the efficiency of translation. Furthermore, we demonstrate that m(6)A modification of mRNAs is co-transcriptional and depends upon the dynamics of the transcribing RNAPII. Suboptimal transcription rates lead to elevated m(6)A content, which may result in reduced translation. This study uncovers a general and widespread link between transcription and translation that is governed by epigenetic modification of mRNAs. Cell Press 2017-04-06 /pmc/articles/PMC5388891/ /pubmed/28388414 http://dx.doi.org/10.1016/j.cell.2017.03.031 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Slobodin, Boris
Han, Ruiqi
Calderone, Vittorio
Vrielink, Joachim A.F. Oude
Loayza-Puch, Fabricio
Elkon, Ran
Agami, Reuven
Transcription Impacts the Efficiency of mRNA Translation via Co-transcriptional N6-adenosine Methylation
title Transcription Impacts the Efficiency of mRNA Translation via Co-transcriptional N6-adenosine Methylation
title_full Transcription Impacts the Efficiency of mRNA Translation via Co-transcriptional N6-adenosine Methylation
title_fullStr Transcription Impacts the Efficiency of mRNA Translation via Co-transcriptional N6-adenosine Methylation
title_full_unstemmed Transcription Impacts the Efficiency of mRNA Translation via Co-transcriptional N6-adenosine Methylation
title_short Transcription Impacts the Efficiency of mRNA Translation via Co-transcriptional N6-adenosine Methylation
title_sort transcription impacts the efficiency of mrna translation via co-transcriptional n6-adenosine methylation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388891/
https://www.ncbi.nlm.nih.gov/pubmed/28388414
http://dx.doi.org/10.1016/j.cell.2017.03.031
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