Differential Repression of Alternative Transcripts: A Screen for miRNA Targets
Identifieur interne : 001423 ( Pmc/Checkpoint ); précédent : 001422; suivant : 001424Differential Repression of Alternative Transcripts: A Screen for miRNA Targets
Auteurs : Matthieu Legendre [France] ; William Ritchie [France] ; Fabrice Lopez [France] ; Daniel Gautheret [France]Source :
- PLoS Computational Biology [ 1553-734X ] ; 2006.
Abstract
Alternative polyadenylation sites produce transcript isoforms with 3′ untranslated regions (UTRs) of different lengths. If a microRNA (miRNA) target is present in the UTR, then only those target-containing isoforms should be sensitive to control by a cognate miRNA. We carried out a systematic examination of 3′ UTRs containing multiple poly(A) sites and putative miRNA targets. Based on expressed sequence tag (EST) counts and EST library information, we observed that levels of isoforms containing targets for miR-1 or miR-124, two miRNAs causing downregulation of transcript levels, were reduced in tissues expressing the corresponding miRNA. This analysis was repeated for all conserved 7-mers in 3′ UTRs, resulting in a selection of 312 motifs. We show that this set is significantly enriched in known miRNA targets and mRNA-destabilizing elements, which validates our initial hypothesis. We scanned the human genome for possible cognate miRNAs and identified phylogenetically conserved precursors matching our motifs. This analysis can help identify target-miRNA couples that went undetected in previous screens, but it may also reveal targets for other types of regulatory factors.
Url:
DOI: 10.1371/journal.pcbi.0020043
PubMed: 16699595
PubMed Central: 1458965
Affiliations:
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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS Comput Biol</journal-id><journal-id journal-id-type="iso-abbrev">PLoS Comput. Biol</journal-id><journal-id journal-id-type="publisher-id">pcbi</journal-id><journal-id journal-id-type="publisher-id">plcb</journal-id><journal-id journal-id-type="pmc">ploscomp</journal-id><journal-title-group><journal-title>PLoS Computational Biology</journal-title></journal-title-group><issn pub-type="ppub">1553-734X</issn><issn pub-type="epub">1553-7358</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">16699595</article-id><article-id pub-id-type="pmc">1458965</article-id><article-id pub-id-type="doi">10.1371/journal.pcbi.0020043</article-id><article-id pub-id-type="publisher-id">05-PLCB-RA-0363R3</article-id><article-id pub-id-type="sici">plcb-02-05-02</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline"><subject>Bioinformatics - Computational Biology</subject></subj-group><subj-group subj-group-type="System Taxonomy"><subject>Mammals</subject></subj-group></article-categories><title-group><article-title>Differential Repression of Alternative Transcripts: A Screen for miRNA Targets</article-title><alt-title alt-title-type="running-head">Alternative Transcript Repression by miRNAs</alt-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Legendre</surname><given-names>Matthieu</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Ritchie</surname><given-names>William</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Lopez</surname><given-names>Fabrice</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Gautheret</surname><given-names>Daniel</given-names></name><xref ref-type="corresp" rid="cor1">*</xref><xref ref-type="aff" rid="aff1"></xref></contrib></contrib-group><aff id="aff1">INSERM ERM 206, Université de la Méditerranée, Marseille, France</aff><contrib-group><contrib contrib-type="editor"><name><surname>Lutz</surname><given-names>Carol</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1">University of Medicine and Dentistry of New Jersey, United States of America</aff><author-notes><corresp id="cor1">* To whom correspondence should be addressed. E-mail: <email>gautheret@esil.univ-mrs.fr</email></corresp></author-notes><pub-date pub-type="ppub"><month>5</month><year>2006</year></pub-date><pub-date pub-type="epub"><day>12</day><month>5</month><year>2006</year></pub-date><pub-date pub-type="epreprint"><day>21</day><month>3</month><year>2006</year></pub-date><volume>2</volume><issue>5</issue><elocation-id>e43</elocation-id><history><date date-type="received"><day>20</day><month>12</month><year>2005</year></date><date date-type="accepted"><day>21</day><month>3</month><year>2006</year></date></history><permissions><copyright-statement> © 2006 Legendre et al.</copyright-statement><copyright-year>2006</copyright-year><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.</license-p></license></permissions><pmc-comment>Differential Repression of Alternative Transcripts: A Screen for miRNA Targets </pmc-comment>
<abstract><p>Alternative polyadenylation sites produce transcript isoforms with 3′ untranslated regions (UTRs) of different lengths. If a microRNA (miRNA) target is present in the UTR, then only those target-containing isoforms should be sensitive to control by a cognate miRNA. We carried out a systematic examination of 3′ UTRs containing multiple poly(A) sites and putative miRNA targets. Based on expressed sequence tag (EST) counts and EST library information, we observed that levels of isoforms containing targets for miR-1 or miR-124, two miRNAs causing downregulation of transcript levels, were reduced in tissues expressing the corresponding miRNA. This analysis was repeated for all conserved 7-mers in 3′ UTRs, resulting in a selection of 312 motifs. We show that this set is significantly enriched in known miRNA targets and mRNA-destabilizing elements, which validates our initial hypothesis. We scanned the human genome for possible cognate miRNAs and identified phylogenetically conserved precursors matching our motifs. This analysis can help identify target-miRNA couples that went undetected in previous screens, but it may also reveal targets for other types of regulatory factors.</p></abstract><abstract abstract-type="synopsis"><title>Synopsis</title><p>MicroRNAs (miRNAs) are short RNA molecules that recognize specific target sequences in the 3′ region of mRNAs. These miRNAs can then specifically keep the mRNAs from being expressed, or translated into proteins. In this article, the authors ask what happens when a targeted mRNA has several forms differing by their 3′ regions. Such 3′ variations are very common. If two or more variations are present in a single mRNA, the result is two or more mRNAs with 3′ ends of different lengths. If an miRNA target is located between the two sites of variability, the shorter transcript should be target free and should escape miRNA-mediated inhibition, while longer transcripts should be inhibited. To test this hypothesis, the authors looked at mRNAs that had these variable 3′ ends. Variants containing targets for certain miRNAs appeared to be specifically underrepresented in tissues where these particular miRNAs are found. This principle was used to find other sequence patterns in 3′ regions that had a similar effect, and a list of 312 significant patterns was obtained. The authors then scanned genome sequences and identified possible cognate miRNAs for these patterns. This new knowledge will help further an understanding of how genes are controlled.</p></abstract><counts><page-count count="10"></page-count></counts><custom-meta-group><custom-meta><meta-name>Citation:</meta-name><meta-value>Legendre M, Ritchie W, Lopez F, Gautheret D (2006) Differential repression of alternative transcripts: A screen for miRNA targets. PLoS Comput Biol 2(5): e43. DOI: <ext-link ext-link-type="doi" xlink:href="10.1371/journal.pcbi.0020043">10.1371/journal.pcbi.0020043</ext-link></meta-value></custom-meta></custom-meta-group></article-meta></front></pmc><affiliations><list><country><li>France</li></country><region><li>Provence-Alpes-Côte d'Azur</li></region><settlement><li>Marseille</li></settlement><orgName><li>Université de la Méditerranée</li></orgName></list><tree><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Legendre, Matthieu" sort="Legendre, Matthieu" uniqKey="Legendre M" first="Matthieu" last="Legendre">Matthieu Legendre</name></region><name sortKey="Gautheret, Daniel" sort="Gautheret, Daniel" uniqKey="Gautheret D" first="Daniel" last="Gautheret">Daniel Gautheret</name><name sortKey="Lopez, Fabrice" sort="Lopez, Fabrice" uniqKey="Lopez F" first="Fabrice" last="Lopez">Fabrice Lopez</name><name sortKey="Ritchie, William" sort="Ritchie, William" uniqKey="Ritchie W" first="William" last="Ritchie">William Ritchie</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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