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dc.contributor.author
Santoro, Raffaella
dc.contributor.author
Lienemann, Philipp
dc.contributor.author
Fussenegger, Martin
dc.date.accessioned
2018-09-06T11:23:41Z
dc.date.available
2017-06-08T21:49:04Z
dc.date.available
2018-09-06T11:23:41Z
dc.date.issued
2009-08-14
dc.identifier.issn
1932-6203
dc.identifier.other
10.1371/journal.pone.0006653
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/15567
dc.identifier.doi
10.3929/ethz-b-000015567
dc.description.abstract
Selection of mammalian high-producer cell lines remains a major challenge for the biopharmaceutical manufacturing industry. Ribosomal RNA (rRNA) genes encode the major component of the ribosome but many rRNA gene copies are not transcribed [1]–[5] due to epigenetic silencing by the nucleolar remodelling complex (NoRC) [6], which may limit the cell's full production capacity. Here we show that the knockdown of TIP5, a subunit of NoRC, decreases the number of silent rRNA genes, upregulates rRNA transcription, enhances ribosome synthesis and increases production of recombinant proteins. However, general enhancement of rRNA transcription rate did not stimulate protein synthesis. Our data demonstrates that the number of transcriptionally competent rRNA genes limits efficient ribosome synthesis. Epigenetic engineering of ribosomal RNA genes offers new possibilities for improving biopharmaceutical manufacturing and provides novel insights into the complex regulatory network which governs the translation machinery in normal cellular processes as well as in pathological conditions like cancer.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Public Library of Science
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/3.0/
dc.title
Epigenetic Engineering of Ribosomal RNA Genes Enhances Protein Production
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 3.0 Unported
ethz.journal.title
PLoS ONE
ethz.journal.volume
4
en_US
ethz.journal.issue
8
en_US
ethz.journal.abbreviated
PLoS ONE
ethz.pages.start
e6653
en_US
ethz.size
7 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.publication.place
Lawrence, KS, USA
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.::03694 - Fussenegger, Martin / Fussenegger, Martin
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.::03694 - Fussenegger, Martin / Fussenegger, Martin
ethz.date.deposited
2017-06-08T21:49:20Z
ethz.source
ECIT
ethz.identifier.importid
imp59364c54e73c469487
ethz.ecitpid
pub:27371
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-20T14:39:11Z
ethz.rosetta.lastUpdated
2018-11-08T01:41:12Z
ethz.rosetta.versionExported
true
ethz.COinS
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