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Cell. 2017 Apr 6;169(2):326-337.e12. doi: 10.1016/j.cell.2017.03.031.

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

Author information

1
Division of Oncogenomics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands. Electronic address: boris.slobodin@gmail.com.
2
Division of Oncogenomics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
3
Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: ranel@tauex.tau.ac.il.
4
Division of Oncogenomics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Department of Genetics, Erasmus University Medical Center, Wytemaweg 80, 3015 CN Rotterdam, the Netherlands. Electronic address: r.agami@nki.nl.

Abstract

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 m6A modification of mRNAs is co-transcriptional and depends upon the dynamics of the transcribing RNAPII. Suboptimal transcription rates lead to elevated m6A 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.

KEYWORDS:

N6-adenosine methylation; RNAPII; TATA; gene regulation; m(6)A; transcription; translation efficiency

PMID:
28388414
PMCID:
PMC5388891
DOI:
10.1016/j.cell.2017.03.031
[Indexed for MEDLINE]
Free PMC Article

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