Many lncRNAs, 5'UTRs, and pseudogenes are translated and some are likely to express functional proteins

  1. Zhe Ji
  2. Ruisheng Song
  3. Aviv Regev
  4. Kevin Struhl  Is a corresponding author
  1. Harvard Medical School, United States
  2. Broad Institute of MIT and Harvard, United States

Abstract

Using a new bioinformatic method to analyze ribosome profiling data, we show that 40% of lncRNAs and pseudogene RNAs expressed in human cells are translated. In addition, ~35% of mRNA coding genes are translated upstream of the primary protein-coding region (uORFs) and 4% are translated downstream (dORFs). Translated lncRNAs preferentially localize in the cytoplasm, whereas untranslated lncRNAs preferentially localize in the nucleus. The translation efficiency of cytoplasmic lncRNAs is nearly comparable to that of mRNAs, suggesting that cytoplasmic lncRNAs are engaged by the ribosome and translated. While most peptides generated from lncRNAs may be highly unstable byproducts without function, ~9% of the peptides are conserved in ORFs in mouse transcripts, as are 74% of pseudogene peptides, 24% of uORF peptides and 32% of dORF peptides. Analyses of synonymous and nonsynonymous substitution rates of these conserved peptides show that some are under stabilizing selection, suggesting potential functional importance.

Article and author information

Author details

  1. Zhe Ji

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
    Competing interests
    No competing interests declared.
  2. Ruisheng Song

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
    Competing interests
    No competing interests declared.
  3. Aviv Regev

    Broad Institute of MIT and Harvard, Cambridge, United States
    Competing interests
    No competing interests declared.
  4. Kevin Struhl

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
    For correspondence
    kevin@hms.harvard.edu
    Competing interests
    Kevin Struhl, Reviewing editor, eLife.

Reviewing Editor

  1. Nahum Sonenberg, McGill University, Canada

Publication history

  1. Received: May 21, 2015
  2. Accepted: December 17, 2015
  3. Accepted Manuscript published: December 19, 2015 (version 1)
  4. Version of Record published: January 21, 2016 (version 2)

Copyright

© 2015, Ji 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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  1. Zhe Ji
  2. Ruisheng Song
  3. Aviv Regev
  4. Kevin Struhl
(2015)
Many lncRNAs, 5'UTRs, and pseudogenes are translated and some are likely to express functional proteins
eLife 4:e08890.
https://doi.org/10.7554/eLife.08890

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