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dc.contributor.authorGulati, Pawanen
dc.contributor.authorAvezov, Edwarden
dc.contributor.authorMa, Marcellaen
dc.contributor.authorAntrobus, Robinen
dc.contributor.authorLehner, Paulen
dc.contributor.authorO'Rahilly, Stephenen
dc.contributor.authorYeo, Gilesen
dc.date.accessioned2014-09-29T10:43:45Z
dc.date.available2014-09-29T10:43:45Z
dc.date.issued2014-09-22en
dc.identifier.citationBioscience Reports 34(5):art:e00144. DOI: 10.1042/BSR20140111en
dc.identifier.issn0144-8463
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/246054
dc.description.abstractSNPs on a chromosome 16 locus encompassing FTO, as well as IRX3, 5, 6, FTM and FTL are robustly associated with human obesity. FTO catalyzes the Fe(II)‐ and 2OG-dependent demethylation of RNA and is an amino acid (AA) sensor that couples AA levels to mTORC1 signaling, thereby playing a key role in regulating growth and translation. However, the cellular compartment in which FTO primarily resides to perform its biochemical role is unclear. Here, we undertake live cell imaging of GFP-FTO, and demonstrate that FTO resides in both the nucleus and cytoplasm. We show using ‘fluorescence loss in photo bleaching’ (FLIP) that a mobile FTO fraction shuttles between both compartments. We performed a proteomic study and identified Exportin 2 (XPO2), one of a family of proteins that mediates the shuttling of proteins between the nucleus and the cytoplasm, as a binding partner of FTO. Finally, using deletion studies, we show that the N-terminus of FTO is required for its ability to shuttle between the nucleus and cytoplasm. In conclusion, FTO is present in both the nucleus and cytoplasm, with a mobile fraction that shuttles between both cellular compartments, possibly by interaction with XPO2.
dc.languageEnglishen
dc.language.isoenen
dc.publisherPortland Press
dc.rightsAttribution 2.0 UK: England & Wales*
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/*
dc.titleFat mass and obesity related (FTO) shuttles between the nucleus and cytoplasmen
dc.typeArticle
dc.description.versionThis is the final published version. It first appeared at http://www.bioscirep.org/bsr/034/bsr034e144.htm.en
prism.numbere00144en
prism.publicationDate2014en
prism.publicationNameBioscience Reportsen
prism.volume34en
dc.rioxxterms.funderMedical Research Council European Commission FP7 Helmholtz Alliance
rioxxterms.versionofrecord10.1042/BSR20140111en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2014-09-22en
dc.contributor.orcidAvezov, Edward [0000-0002-2894-0585]
dc.contributor.orcidLehner, Paul [0000-0001-9383-1054]
dc.contributor.orcidO'Rahilly, Stephen [0000-0003-2199-4449]
dc.contributor.orcidYeo, Giles [0000-0001-8823-3615]
dc.identifier.eissn1573-4935
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMEDICAL RESEARCH COUNCIL (G0900554)
pubs.funder-project-idMRC (MC_UU_12012/1)
pubs.funder-project-idMRC (MC_UU_12012/5)
pubs.funder-project-idWellcome Trust (101835/Z/13/Z)
pubs.funder-project-idMedical Research Council (MC_UU_12012/5/B)
pubs.funder-project-idWellcome Trust (095515/Z/11/Z)
pubs.funder-project-idWellcome Trust (100574/Z/12/Z)
pubs.funder-project-idWellcome Trust (100140/Z/12/Z)
pubs.funder-project-idEC FP7 CP (266408)


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales