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Elife. 2015 Dec 19;4:e08890. doi: 10.7554/eLife.08890.

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

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Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States.
Broad Institute of MIT and Harvard, Cambridge, United States.
Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, United States.


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.


5'UTR; biological function; cell biology; evolutionary biology; genomics; human; non-coding RNAs; pseudogene; ribosome profiling; translation

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