68
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Long noncoding RNAs are rarely translated in two human cell lines

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Related collections

          Most cited references47

          • Record: found
          • Abstract: not found
          • Article: not found

          Random Forests

            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            An Integrated Encyclopedia of DNA Elements in the Human Genome

            Summary The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure, and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall the project provides new insights into the organization and regulation of our genes and genome, and an expansive resource of functional annotations for biomedical research.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Universal sample preparation method for proteome analysis.

              We describe a method, filter-aided sample preparation (FASP), which combines the advantages of in-gel and in-solution digestion for mass spectrometry-based proteomics. We completely solubilized the proteome in sodium dodecyl sulfate, which we then exchanged by urea on a standard filtration device. Peptides eluted after digestion on the filter were pure, allowing single-run analyses of organelles and an unprecedented depth of proteome coverage.
                Bookmark

                Author and article information

                Journal
                Genome Res
                Genome Res
                GENOME
                Genome Research
                Cold Spring Harbor Laboratory Press
                1088-9051
                1549-5469
                September 2012
                September 2012
                : 22
                : 9
                : 1646-1657
                Affiliations
                [1 ]Department of Statistics, University of California, Berkeley, California 94720, USA;
                [2 ]Center for Molecular Medicine and Genetics, School of Medicine, Wayne State University, Detroit, Michigan 48201, USA;
                [3 ]Biomolecular Research Center, Boise State University, Boise, Idaho 83725, USA;
                [4 ]Department of Computer Science, Stanford University, Palo Alto, California 94305, USA;
                [5 ]University of North Carolina School of Medicine, Chapel Hill, North Carolina 29425, USA;
                [6 ]College of Arts and Sciences, Boise State University, Boise, Idaho 83725, USA
                Author notes
                [7]

                These authors contributed equally to this work.

                Article
                9518021
                10.1101/gr.134767.111
                3431482
                22955977
                d917d0d2-6a8b-476a-af1e-35e6bd59a4ec
                © 2012, Published by Cold Spring Harbor Laboratory Press

                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/.

                History
                : 11 November 2011
                : 3 May 2012
                Categories
                Research

                Comments

                Comment on this article