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

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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.

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Zhe Ji

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States

Competing interests
No competing interests declared.
Ruisheng Song

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States

Competing interests
No competing interests declared.
Aviv Regev

Broad Institute of MIT and Harvard, Cambridge, United States

Competing interests
No competing interests declared.
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.

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