Human selenoprotein P and S variant mRNAs with different numbers of SECIS elements and inferences from mutant mice of the roles of multiple SECIS elements

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dc.contributor.authorWu, Sen
dc.contributor.authorMariotti, Marco
dc.contributor.authorSantesmasses, Didac
dc.contributor.authorHill, Kristina E.
dc.contributor.authorBaclaocos, Janinah
dc.contributor.authorAparicio-Prat, Estel
dc.contributor.authorLi, Shuping
dc.contributor.authorMackrill, John
dc.contributor.authorWu, Yuanyuan
dc.contributor.authorHoward, Michael T.
dc.contributor.authorCapecchi, Mario
dc.contributor.authorGuigó, Roderic
dc.contributor.authorBurk, Raymond F.
dc.contributor.authorAtkins, John F.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderMinistry of Agriculture of the People's Republic of Chinaen
dc.contributor.funderNational Institutes of Healthen
dc.contributor.funderHoward Hughes Medical Instituteen
dc.contributor.funderEMBOen
dc.date.accessioned2018-03-28T14:55:57Z
dc.date.available2018-03-28T14:55:57Z
dc.date.issued2016-11-23
dc.date.updated2018-03-28T14:44:54Z
dc.description.abstractDynamic redefinition of the 10 UGAs in human and mouse selenoprotein P (Sepp1) mRNAs to specify selenocysteine instead of termination involves two 3′ UTR structural elements (SECIS) and is regulated by selenium availability. In addition to the previously known human Sepp1 mRNA poly(A) addition site just 3′ of SECIS 2, two further sites were identified with one resulting in 10–25% of the mRNA lacking SECIS 2. To address function, mutant mice were generated with either SECIS 1 or SECIS 2 deleted or with the first UGA substituted with a serine codon. They were fed on either high or selenium-deficient diets. The mutants had very different effects on the proportions of shorter and longer product Sepp1 protein isoforms isolated from plasma, and on viability. Spatially and functionally distinctive effects of the two SECIS elements on UGA decoding were inferred. We also bioinformatically identify two selenoprotein S mRNAs with different 5′ sequences predicted to yield products with different N-termini. These results provide insights into SECIS function and mRNA processing in selenoprotein isoform diversity.en
dc.description.sponsorshipMinistry of Agriculture of the People's Republic of China (Transgenic Research Grant 2014ZX0801014B); National Institutes of Health (NIH grant nos. R37ES02497, R01GM114291 and R21ES022716); EMBO (short-term EMBO fellowship)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationWu, S., Mariotti, M., Santesmasses, D., Hill, K. E., Baclaocos, J., Aparicio-Prat, E., Li, S., Mackrill, J., Wu, Y., Howard, M. T., Capecchi, M., Guigó, R., Burk, R. F. and Atkins, J. F. (2016) 'Human selenoprotein P and S variant mRNAs with different numbers of SECIS elements and inferences from mutant mice of the roles of multiple SECIS elements', Open Biology, 6(11), 160241 (16 pp). doi: 10.1098/rsob.160241en
dc.identifier.doi10.1098/rsob.160241
dc.identifier.endpage160241-16en
dc.identifier.issn2046-2441
dc.identifier.issued11en
dc.identifier.journaltitleOpen Biologyen
dc.identifier.startpage160241-1en
dc.identifier.urihttps://hdl.handle.net/10468/5714
dc.identifier.volume6en
dc.language.isoenen
dc.publisherThe Royal Societyen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Investigator Programme/13/IA/1853/IE/Dynamic redefinition of codons: From antivirals to an essential micronutrient/en
dc.relation.urihttp://rsob.royalsocietypublishing.org/content/royopenbio/6/11/160241.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.subjectCodon redefinitionen
dc.subjectRibosome specializationen
dc.subjectSelenocysteineen
dc.subjectSelenoprotein Pen
dc.subjectSelenoprotein Sen
dc.subjectGeneticsen
dc.subjectMolecular biologyen
dc.subjectCellular biologyen
dc.subjectBioinformaticsen
dc.titleHuman selenoprotein P and S variant mRNAs with different numbers of SECIS elements and inferences from mutant mice of the roles of multiple SECIS elementsen
dc.typeArticle (peer-reviewed)en
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