1. Cell Biology
  2. Chromosomes and Gene Expression
Download icon

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
Research Article
  • Cited 228
  • Views 10,948
  • Annotations
Cite this article as: eLife 2015;4:e08890 doi: 10.7554/eLife.08890


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
    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)


© 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.


  • 10,948
    Page views
  • 2,447
  • 228

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Cell Biology
    2. Neuroscience
    Amit Kumar et al.
    Research Article Updated

    Hypoxic adaptation mediated by HIF transcription factors requires mitochondria, which have been implicated in regulating HIF1α stability in hypoxia by distinct models that involve consuming oxygen or alternatively converting oxygen into the second messenger peroxide. Here, we use a ratiometric, peroxide reporter, HyPer to evaluate the role of peroxide in regulating HIF1α stability. We show that antioxidant enzymes are neither homeostatically induced nor are peroxide levels increased in hypoxia. Additionally, forced expression of diverse antioxidant enzymes, all of which diminish peroxide, had disparate effects on HIF1α protein stability. Moreover, decrease in lipid peroxides by glutathione peroxidase-4 or superoxide by mitochondrial SOD, failed to influence HIF1α protein stability. These data show that mitochondrial, cytosolic or lipid ROS were not necessary for HIF1α stability, and favor a model where mitochondria contribute to hypoxic adaptation as oxygen consumers.

    1. Cell Biology
    2. Developmental Biology
    Shaun Abrams, Jeremy F Reiter
    Research Article

    Craniofacial defects are among the most common phenotypes caused by ciliopathies, yet the developmental and molecular etiology of these defects is poorly understood. We investigated multiple mouse models of human ciliopathies (including Tctn2, Cc2d2a and Tmem231 mutants) and discovered that each displays hypotelorism, a narrowing of the midface. As early in development as the end of gastrulation, Tctn2 mutants displayed reduced activation of the Hedgehog (HH) pathway in the prechordal plate, the head organizer. This prechordal plate defect preceded a reduction of HH pathway activation and Shh expression in the adjacent neurectoderm. Concomitant with the reduction of HH pathway activity, Tctn2 mutants exhibited increased cell death in the neurectoderm and facial ectoderm, culminating in a collapse of the facial midline. Enhancing HH signaling by decreasing the gene dosage of a negative regulator of the pathway, Ptch1, decreased cell death and rescued the midface defect in both Tctn2 and Cc2d2a mutants. These results reveal that ciliary HH signaling mediates communication between the prechordal plate and the neurectoderm to provide cellular survival cues essential for development of the facial midline.