Cap-proximal nucleotides via differential eIF4E binding and alternative promoter usage mediate translational response to energy stress

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Cite this article as: eLife 2017;6:e21907 doi: 10.7554/eLife.21907

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Abstract

Transcription start-site (TSS) selection and alternative promoter (AP) usage contribute to gene expression complexity but little is known about their impact on translation. Here we performed TSS mapping of the translatome following energy stress. Assessing the contribution of cap-proximal TSS nucleotides, we found dramatic effect on translation only upon stress. As eIF4E levels were reduced, we determined its binding to capped-RNAs with different initiating nucleotides and found the lowest affinity to 5'cytidine in correlation with the translational stress-response. In addition, the number of differentially translated APs was elevated following stress. These include novel glucose starvation-induced downstream transcripts for the translation regulators eIF4A and Pabp, which are also translationally-induced despite general translational inhibition. The resultant eIF4A protein is N-terminally truncated and acts as eIF4A inhibitor. The induced Pabp isoform has shorter 5'UTR removing an auto-inhibitory element. Our findings uncovered several levels of coordination of transcription and translation responses to energy stress.

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Author details

Ana Tamarkin-Ben-Harush

Department of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot, Israel

Competing interests
The authors declare that no competing interests exist.
Jean-Jacques Vasseur

Department of Nucleic Acids, BMM UMR 5247, CNRS-Université Montpellier-ENSCM, Montpellier, France

Competing interests
The authors declare that no competing interests exist.
Françoise Debart

Department of Nucleic Acids, IBMM UMR 5247, CNRS-Université Montpellier-ENSCM, Montpellier, France

Competing interests
The authors declare that no competing interests exist.
Igor Ulitsky

Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel

For correspondence
igor.ulitsky@weizmann.ac.il

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0555-6561
Rivka Dikstein

Department of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot, Israel

For correspondence
rivka.dikstein@weizmann.ac.il

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-6251-4723

Funding

Israel Academy of Sciences and Humanities

Igor Ulitsky
Rivka Dikstein

Minerva Foundation

Igor Ulitsky
Rivka Dikstein

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

Timothy W Nilsen, Case Western Reserve University, United States

Publication history

Received: September 28, 2016
Accepted: January 20, 2017
Accepted Manuscript published: February 8, 2017 (version 1)
Version of Record published: February 14, 2017 (version 2)

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.