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dc.contributor.authorGandin, Valentinaen_US
dc.contributor.authorMasvidal, Laiaen_US
dc.contributor.authorHulea, Lauraen_US
dc.contributor.authorGravel, Simon-Pierreen_US
dc.contributor.authorCargnello, Marieen_US
dc.contributor.authorMcLaughlan, Shannonen_US
dc.contributor.authorCai, Yutianen_US
dc.contributor.authorBalanathan, Preetikaen_US
dc.contributor.authorMorita, Masahiroen_US
dc.contributor.authorRajakumar, Arjunaen_US
dc.contributor.authorFuric, Lucen_US
dc.contributor.authorPollak, Michaelen_US
dc.contributor.authorPorco, John A.en_US
dc.contributor.authorSt-Pierre, Julieen_US
dc.contributor.authorPelletier, Jerryen_US
dc.contributor.authorLarsson, Olaen_US
dc.contributor.authorTopisirovic, Ivanen_US
dc.coverage.spatialUnited Statesen_US
dc.date2016-03-14
dc.date.accessioned2018-01-30T16:27:59Z
dc.date.available2018-01-30T16:27:59Z
dc.date.issued2016-03-14
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/26984228
dc.identifier.citationValentina Gandin, Laia Masvidal, Laura Hulea, Simon-Pierre Gravel, Marie Cargnello, Shannon McLaughlan, Yutian Cai, Preetika Balanathan, Masahiro Morita, Arjuna Rajakumar, Luc Furic, Michael Pollak, John A Porco, Julie St-Pierre, Jerry Pelletier, Ola Larsson, Ivan Topisirovic. "nanoCAGE reveals 5' UTR features that define specific modes of translation of functionally related MTOR-sensitive mRNAs.." Genome Res, Volume 26, Issue 5, pp. 636 - 648.
dc.identifier.issn1549-5469
dc.identifier.urihttps://hdl.handle.net/2144/26488
dc.description.abstractThe diversity of MTOR-regulated mRNA translation remains unresolved. Whereas ribosome-profiling suggested that MTOR almost exclusively stimulates translation of the TOP (terminal oligopyrimidine motif) and TOP-like mRNAs, polysome-profiling indicated that MTOR also modulates translation of mRNAs without the 5' TOP motif (non-TOP mRNAs). We demonstrate that in ribosome-profiling studies, detection of MTOR-dependent changes in non-TOP mRNA translation was obscured by low sensitivity and methodology biases. Transcription start site profiling using nano-cap analysis of gene expression (nanoCAGE) revealed that not only do many MTOR-sensitive mRNAs lack the 5' TOP motif but that 5' UTR features distinguish two functionally and translationally distinct subsets of MTOR-sensitive mRNAs: (1) mRNAs with short 5' UTRs enriched for mitochondrial functions, which require EIF4E but are less EIF4A1-sensitive; and (2) long 5' UTR mRNAs encoding proliferation- and survival-promoting proteins, which are both EIF4E- and EIF4A1-sensitive. Selective inhibition of translation of mRNAs harboring long 5' UTRs via EIF4A1 suppression leads to sustained expression of proteins involved in respiration but concomitant loss of those protecting mitochondrial structural integrity, resulting in apoptosis. Conversely, simultaneous suppression of translation of both long and short 5' UTR mRNAs by MTOR inhibitors results in metabolic dormancy and a predominantly cytostatic effect. Thus, 5' UTR features define different modes of MTOR-sensitive translation of functionally distinct subsets of mRNAs, which may explain the diverse impact of MTOR and EIF4A inhibitors on neoplastic cells.en_US
dc.description.sponsorshipP50 GM067041 - NIGMS NIH HHS; R01 GM073855 - NIGMS NIH HHSen_US
dc.format.extent636 - 648en_US
dc.languageengen_US
dc.relation.ispartofGenome Resen_US
dc.rights© 2016 Gandin et al.; Published by Cold Spring Harbor Laboratory Press This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectScience & technologyen_US
dc.subjectLife sciences & biomedicineen_US
dc.subjectBiochemistry & molecular biologyen_US
dc.subjectBiotechnology & applied microbiologyen_US
dc.subjectGenetics & heredityen_US
dc.subjectGenome-wide analysisen_US
dc.subjectEukaryotic translationen_US
dc.subjectMammalian translationen_US
dc.subjectProtein synthesisen_US
dc.subject5' untranslated regionsen_US
dc.subjectApoptosisen_US
dc.subjectEukaryotic initiation factor-4E (EIF4A)en_US
dc.subjectFemaleen_US
dc.subjectHumansen_US
dc.subjectMCF-7 Cellsen_US
dc.subjectProtein biosynthesisen_US
dc.subjectTOR serine-threonine kinasesen_US
dc.subjectBiological sciencesen_US
dc.subjectMedical and health sciencesen_US
dc.subjectBioinformaticsen_US
dc.titlenanoCAGE reveals 5' UTR features that define specific modes of translation of functionally related MTOR-sensitive mRNAsen_US
dc.typeArticle
dc.identifier.doi10.1101/gr.197566.115
pubs.elements-sourcepubmeden_US
pubs.notesEmbargo: Not knownen_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, College of Arts & Sciencesen_US
pubs.organisational-groupBoston University, College of Arts & Sciences, Department of Chemistryen_US
pubs.publication-statusPublisheden_US


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© 2016 Gandin et al.; Published by Cold Spring Harbor Laboratory Press

This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
Except where otherwise noted, this item's license is described as © 2016 Gandin et al.; Published by Cold Spring Harbor Laboratory Press This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.