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dc.contributor.authorCourtes, Franck C.
dc.contributor.authorGu, Chen
dc.contributor.authorWong, Niki S.C.
dc.contributor.authorDedon, Peter C.
dc.contributor.authorYap, Miranda G.S.
dc.contributor.authorLee, Dong-Yup
dc.date.accessioned2015-10-15T12:23:47Z
dc.date.available2015-10-15T12:23:47Z
dc.date.issued2014-01
dc.date.submitted2014-01
dc.identifier.issn01681656
dc.identifier.urihttp://hdl.handle.net/1721.1/99335
dc.description.abstractThe mTOR pathway is a conserved master regulator of translational activity that influences the fate of industrially relevant CHO cell cultures, yet its molecular mechanisms remain unclear. Interestingly, rapamycin specific inhibition of the mTOR pathway in CHO cells was found to down-regulate the small nucleolar RNA U19 (snoRNA U19) by 2-fold via translatome profiling. snoRNA U19 guides the two most conserved pseudouridylation modifications on 28S ribosomal RNA (rRNA) that are important for the biogenesis and proper function of ribosomes. In order to further understand the role of snoRNA U19 as a potential player in the mTOR pathway, we measured 28S rRNA pseudouridylation upon rapamycin treatments and/or snoRNA U19 overexpression conditions, thereby characterizing the subsequent effects on ribosome efficiency and global translation by polysome profiling. We showed that 28S rRNA pseudouridylation was increased by rapamycin treatment and/or overexpression of snoRNA U19, but only the latter condition improved ribosome efficiency toward higher global translation, thus implying that the mTOR pathway induces pseudouridylation at different sites along the 28S rRNA possibly with either positive or negative effects on the cellular phenotype. This discovery of snoRNA U19 as a new downstream effector of the mTOR pathway suggests that cell engineering of snoRNAs can be used to regulate translation and improve cellular growth in CHO cell cultures in the future.en_US
dc.description.sponsorshipNational University of Singaporeen_US
dc.description.sponsorshipSingapore. Agency for Science, Technology and Researchen_US
dc.description.sponsorshipKorea (South). Rural Development Administration. Next-Generation BioGreen 21 Program (SSAC PJ009520)en_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.jbiotec.2014.01.024en_US
dc.rightsCreative Commons Attributionen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.title28S rRNA is inducibly pseudouridylated by the mTOR pathway translational control in CHO cell culturesen_US
dc.typeArticleen_US
dc.identifier.citationCourtes, Franck C., Chen Gu, Niki S.C. Wong, Peter C. Dedon, Miranda G.S. Yap, and Dong-Yup Lee. “28S rRNA Is Inducibly Pseudouridylated by the mTOR Pathway Translational Control in CHO Cell Cultures.” Journal of Biotechnology 174 (March 2014): 16–21.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Center for Environmental Health Sciencesen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.mitauthorGu, Chenen_US
dc.contributor.mitauthorDedon, Peter C.en_US
dc.relation.journalJournal of Biotechnologyen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsCourtes, Franck C.; Gu, Chen; Wong, Niki S.C.; Dedon, Peter C.; Yap, Miranda G.S.; Lee, Dong-Yupen_US
dc.identifier.orcidhttps://orcid.org/0000-0003-0011-3067
dc.identifier.orcidhttps://orcid.org/0000-0001-9920-2080
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


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