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

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 (...

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Main Authors: Zhe Ji, Ruisheng Song, Aviv Regev, Kevin Struhl
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2015-12-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/08890
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author Zhe Ji
Ruisheng Song
Aviv Regev
Kevin Struhl
author_facet Zhe Ji
Ruisheng Song
Aviv Regev
Kevin Struhl
author_sort Zhe Ji
collection DOAJ
description 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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spelling doaj.art-34c825865e8c4c33b2f87ba73e41549b2022-12-22T02:05:18ZengeLife Sciences Publications LtdeLife2050-084X2015-12-01410.7554/eLife.08890Many lncRNAs, 5’UTRs, and pseudogenes are translated and some are likely to express functional proteinsZhe Ji0Ruisheng Song1https://orcid.org/0000-0002-6856-4721Aviv Regev2Kevin Struhl3Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States; Broad Institute of MIT and Harvard, Cambridge, United StatesDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United StatesBroad Institute of MIT and Harvard, Cambridge, United States; Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, United StatesDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United StatesUsing 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.https://elifesciences.org/articles/08890non-coding RNAtranslationribosome profiling5'UTRpseudogenebiological function
spellingShingle Zhe Ji
Ruisheng Song
Aviv Regev
Kevin Struhl
Many lncRNAs, 5’UTRs, and pseudogenes are translated and some are likely to express functional proteins
eLife
non-coding RNA
translation
ribosome profiling
5'UTR
pseudogene
biological function
title Many lncRNAs, 5’UTRs, and pseudogenes are translated and some are likely to express functional proteins
title_full Many lncRNAs, 5’UTRs, and pseudogenes are translated and some are likely to express functional proteins
title_fullStr Many lncRNAs, 5’UTRs, and pseudogenes are translated and some are likely to express functional proteins
title_full_unstemmed Many lncRNAs, 5’UTRs, and pseudogenes are translated and some are likely to express functional proteins
title_short Many lncRNAs, 5’UTRs, and pseudogenes are translated and some are likely to express functional proteins
title_sort many lncrnas 5 utrs and pseudogenes are translated and some are likely to express functional proteins
topic non-coding RNA
translation
ribosome profiling
5'UTR
pseudogene
biological function
url https://elifesciences.org/articles/08890
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AT ruishengsong manylncrnas5utrsandpseudogenesaretranslatedandsomearelikelytoexpressfunctionalproteins
AT avivregev manylncrnas5utrsandpseudogenesaretranslatedandsomearelikelytoexpressfunctionalproteins
AT kevinstruhl manylncrnas5utrsandpseudogenesaretranslatedandsomearelikelytoexpressfunctionalproteins