Long noncoding RNAs are rarely translated in two human cell lines
- Balázs Bánfai1,7,
- Hui Jia2,7,
- Jainab Khatun3,7,
- Emily Wood2,
- Brian Risk3,
- William E. Gundling Jr.2,
- Anshul Kundaje4,
- Harsha P. Gunawardena5,
- Yanbao Yu5,
- Ling Xie5,
- Krzysztof Krajewski5,
- Brian D. Strahl5,
- Xian Chen5,
- Peter Bickel1,
- Morgan C. Giddings6,
- James B. Brown1,7,8 and
- Leonard Lipovich2,7,8
- 1Department of Statistics, University of California, Berkeley, California 94720, USA;
- 2Center for Molecular Medicine and Genetics, School of Medicine, Wayne State University, Detroit, Michigan 48201, USA;
- 3Biomolecular Research Center, Boise State University, Boise, Idaho 83725, USA;
- 4Department of Computer Science, Stanford University, Palo Alto, California 94305, USA;
- 5University of North Carolina School of Medicine, Chapel Hill, North Carolina 29425, USA;
- 6College of Arts and Sciences, Boise State University, Boise, Idaho 83725, USA
-
↵7 These authors contributed equally to this work.
Abstract
Data from the Encyclopedia of DNA Elements (ENCODE) project show over 9640 human genome loci classified as long noncoding RNAs (lncRNAs), yet only ∼100 have been deeply characterized to determine their role in the cell. To measure the protein-coding output from these RNAs, we jointly analyzed two recent data sets produced in the ENCODE project: tandem mass spectrometry (MS/MS) data mapping expressed peptides to their encoding genomic loci, and RNA-seq data generated by ENCODE in long polyA+ and polyA− fractions in the cell lines K562 and GM12878. We used the machine-learning algorithm RuleFit3 to regress the peptide data against RNA expression data. The most important covariate for predicting translation was, surprisingly, the Cytosol polyA− fraction in both cell lines. LncRNAs are ∼13-fold less likely to produce detectable peptides than similar mRNAs, indicating that ∼92% of GENCODE v7 lncRNAs are not translated in these two ENCODE cell lines. Intersecting 9640 lncRNA loci with 79,333 peptides yielded 85 unique peptides matching 69 lncRNAs. Most cases were due to a coding transcript misannotated as lncRNA. Two exceptions were an unprocessed pseudogene and a bona fide lncRNA gene, both with open reading frames (ORFs) compromised by upstream stop codons. All potentially translatable lncRNA ORFs had only a single peptide match, indicating low protein abundance and/or false-positive peptide matches. We conclude that with very few exceptions, ribosomes are able to distinguish coding from noncoding transcripts and, hence, that ectopic translation and cryptic mRNAs are rare in the human lncRNAome.
Footnotes
-
↵8 Corresponding authors
E-mail benbrownofberkeley{at}gmail.com
E-mail llipovich{at}med.wayne.edu
-
[Supplemental material is available for this article.]
-
Article and supplemental material are at http://www.genome.org/cgi/doi/10.1101/gr.134767.111.
Freely available online through the Genome Research Open Access option.
- Received November 11, 2011.
- Accepted May 3, 2012.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/.
