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Conservation of uORF repressiveness and sequence features in mouse, human and zebrafish

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  • Guo-Liang Chew

    (Harvard University
    Present address: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA)

  • Andrea Pauli

    (Harvard University
    Present address: Research Institute of Molecular Pathology (IMP), 1030 Vienna, Austria)

  • Alexander F. Schier

    (Harvard University
    The Broad Institute of Massachusetts Institute of Technology and Harvard
    FAS Center for Systems Biology, Harvard University
    Center for Brain Science, Harvard University)

Abstract

Upstream open reading frames (uORFs) are ubiquitous repressive genetic elements in vertebrate mRNAs. While much is known about the regulation of individual genes by their uORFs, the range of uORF-mediated translational repression in vertebrate genomes is largely unexplored. Moreover, it is unclear whether the repressive effects of uORFs are conserved across species. To address these questions, we analyse transcript sequences and ribosome profiling data from human, mouse and zebrafish. We find that uORFs are depleted near coding sequences (CDSes) and have initiation contexts that diminish their translation. Linear modelling reveals that sequence features at both uORFs and CDSes modulate the translation of CDSes. Moreover, the ratio of translation over 5′ leaders and CDSes is conserved between human and mouse, and correlates with the number of uORFs. These observations suggest that the prevalence of vertebrate uORFs may be explained by their conserved role in repressing CDS translation.

Suggested Citation

  • Guo-Liang Chew & Andrea Pauli & Alexander F. Schier, 2016. "Conservation of uORF repressiveness and sequence features in mouse, human and zebrafish," Nature Communications, Nature, vol. 7(1), pages 1-10, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11663
    DOI: 10.1038/ncomms11663
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    Cited by:

    1. Haiwang Yang & Qianru Li & Emily K. Stroup & Sheng Wang & Zhe Ji, 2024. "Widespread stable noncanonical peptides identified by integrated analyses of ribosome profiling and ORF features," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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