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dc.contributor.author
Galgano, Alessia
dc.contributor.author
Forrer, Michael
dc.contributor.author
Jaskiewicz, Lukasz
dc.contributor.author
Kanitz, Alexander
dc.contributor.author
Zavolan, Mihaela
dc.contributor.author
Gerber, André P.
dc.date.accessioned
2018-08-09T12:53:02Z
dc.date.available
2017-06-08T20:12:18Z
dc.date.available
2018-08-09T12:53:02Z
dc.date.issued
2008-09-08
dc.identifier.issn
1932-6203
dc.identifier.other
10.1371/journal.pone.0003164
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/11224
dc.identifier.doi
10.3929/ethz-b-000011224
dc.description.abstract
Genome-wide identification of mRNAs regulated by RNA-binding proteins is crucial to uncover post-transcriptional gene regulatory systems. The conserved PUF family RNA-binding proteins repress gene expression post-transcriptionally by binding to sequence elements in 3′-UTRs of mRNAs. Despite their well-studied implications for development and neurogenesis in metazoa, the mammalian PUF family members are only poorly characterized and mRNA targets are largely unknown. We have systematically identified the mRNAs associated with the two human PUF proteins, PUM1 and PUM2, by the recovery of endogenously formed ribonucleoprotein complexes and the analysis of associated RNAs with DNA microarrays. A largely overlapping set comprised of hundreds of mRNAs were reproducibly associated with the paralogous PUM proteins, many of them encoding functionally related proteins. A characteristic PUF-binding motif was highly enriched among PUM bound messages and validated with RNA pull-down experiments. Moreover, PUF motifs as well as surrounding sequences exhibit higher conservation in PUM bound messages as opposed to transcripts that were not found to be associated, suggesting that PUM function may be modulated by other factors that bind conserved elements. Strikingly, we found that PUF motifs are enriched around predicted miRNA binding sites and that high-confidence miRNA binding sites are significantly enriched in the 3′-UTRs of experimentally determined PUM1 and PUM2 targets, strongly suggesting an interaction of human PUM proteins with the miRNA regulatory system. Our work suggests extensive connections between the RBP and miRNA post-transcriptional regulatory systems and provides a framework for deciphering the molecular mechanism by which PUF proteins regulate their target mRNAs.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Public Library of Science (PLoS)
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/3.0/
dc.title
Comparative analysis of mRNA targets for human PUF-family proteins suggests extensive interaction with the miRNA regulatory system
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 3.0 Unported
ethz.journal.title
PLoS ONE
ethz.journal.volume
3
en_US
ethz.journal.issue
9
en_US
ethz.journal.abbreviated
PLoS ONE
ethz.pages.start
e3164
en_US
ethz.size
16 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.notes
Received July 11 2008, Accepted August 18 2008, Also published by: PubMed Central, s.l..
en_US
ethz.publication.place
Lawrence
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03683 - Detmar, Michael / Detmar, Michael
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03683 - Detmar, Michael / Detmar, Michael
ethz.date.deposited
2017-06-08T20:12:40Z
ethz.source
ECIT
ethz.identifier.importid
imp59364bffaba0871331
ethz.ecitpid
pub:22358
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-19T09:30:30Z
ethz.rosetta.lastUpdated
2018-11-07T23:15:11Z
ethz.rosetta.versionExported
true
ethz.COinS
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