1. Biochemistry and Chemical Biology
  2. Chromosomes and Gene Expression
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Cap-proximal nucleotides via differential eIF4E binding and alternative promoter usage mediate translational response to energy stress

  1. Ana Tamarkin-Ben-Harush
  2. Jean-Jacques Vasseur
  3. Françoise Debart
  4. Igor Ulitsky  Is a corresponding author
  5. Rivka Dikstein  Is a corresponding author
  1. The Weizmann Institute of Science, Israel
  2. BMM UMR 5247, CNRS-Université Montpellier-ENSCM, France
  3. IBMM UMR 5247, CNRS-Université Montpellier-ENSCM, France
Research Article
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Cite this article as: eLife 2017;6:e21907 doi: 10.7554/eLife.21907

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.

Article and author information

Author details

  1. 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.
  2. 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.
  3. 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.
  4. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0555-6561
  5. 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.
    ORCID icon "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

  1. Timothy W Nilsen, Case Western Reserve University, United States

Publication history

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

Copyright

© 2017, Tamarkin-Ben-Harush et al.

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.

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