Systematic analysis of the PTEN 5' leader identifies a major AUU initiated proteoform

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dc.contributor.authorTzani, Ioanna
dc.contributor.authorIvanov, Ivaylo P.
dc.contributor.authorAndreev, Dmitry E.
dc.contributor.authorDmitriev, Ruslan I.
dc.contributor.authorDean, Kellie
dc.contributor.authorBaranov, Pavel V.
dc.contributor.authorAtkins, John F.
dc.contributor.authorLoughran, Gary
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderHealth Research Boarden
dc.contributor.funderRussian Science Foundationen
dc.date.accessioned2018-03-28T15:26:51Z
dc.date.available2018-03-28T15:26:51Z
dc.date.issued2016-05-25
dc.date.updated2018-03-28T15:13:38Z
dc.description.abstractAbundant evidence for translation within the 5′ leaders of many human genes is rapidly emerging, especially, because of the advent of ribosome profiling. In most cases, it is believed that the act of translation rather than the encoded peptide is important. However, the wealth of available sequencing data in recent years allows phylogenetic detection of sequences within 5′ leaders that have emerged under coding constraint and therefore allow for the prediction of functional 5′ leader translation. Using this approach, we previously predicted a CUG-initiated, 173 amino acid N-terminal extension to the human tumour suppressor PTEN. Here, a systematic experimental analysis of translation events in the PTEN 5′ leader identifies at least two additional non-AUG-initiated PTEN proteoforms that are expressed in most human cell lines tested. The most abundant extended PTEN proteoform initiates at a conserved AUU codon and extends the canonical AUG-initiated PTEN by 146 amino acids. All N-terminally extended PTEN proteoforms tested retain the ability to downregulate the PI3K pathway. We also provide evidence for the translation of two conserved AUG-initiated upstream open reading frames within the PTEN 5′ leader that control the ratio of PTEN proteoforms.en
dc.description.sponsorshipHealth Research Board (PhD/2007/04); Russian Science Foundation (14-14-00127)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationTzani, I., Ivanov, I. P., Andreev, D. E., Dmitriev, R. I., Dean, K. A., Baranov, P. V., Atkins, J. F. and Loughran, G. (2016) 'Systematic analysis of the PTEN 5' leader identifies a major AUU initiated proteoform', Open Biology, 6(5), 150203 (13pp). doi: 10.1098/rsob.150203en
dc.identifier.doi10.1098/rsob.150203
dc.identifier.endpage150203-13en
dc.identifier.issn2046-2441
dc.identifier.issued5en
dc.identifier.journaltitleOpen Biologyen
dc.identifier.startpage150203-1en
dc.identifier.urihttps://hdl.handle.net/10468/5715
dc.identifier.volume6en
dc.language.isoenen
dc.publisherThe Royal Societyen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Starting Investigator Research Grant (SIRG)/13/SIRG/2144/IE/Development of Bionic Sensor Materials for Metabolic Imaging in Regenerative Medicine/en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Investigator Programme/12/IA/1335/IE/Development of computational resources for the analysis of Genome Wide Information on Protein Synthesis (GWIPS)./en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Investigator Programme/12/IA/1335/IE/Development of computational resources for the analysis of Genome Wide Information on Protein Synthesis (GWIPS)./en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Principal Investigator Programme (PI)/08/IN.1/B1889/IE/Altered Genetic Code Readout/en
dc.relation.urihttp://rsob.royalsocietypublishing.org/content/royopenbio/6/5/150203.full.pdf
dc.rights© 2016 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectPTEN-Len
dc.subjectnon-AUGen
dc.subjectAUUen
dc.subjectuORFen
dc.subjectMolecular biologyen
dc.titleSystematic analysis of the PTEN 5' leader identifies a major AUU initiated proteoformen
dc.typeArticle (peer-reviewed)en
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