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.author Wu, Sen
• dc.contributor.author Mariotti, Marco, 1984-
• dc.contributor.author Santesmasses Ruiz, Didac, 1978-
• dc.contributor.author Hill, Kristina E.
• dc.contributor.author Baclaocos, Janinah
• dc.contributor.author Aparicio i Prat, Estel, 1986-
• dc.contributor.author Li, Shuping
• dc.contributor.author Mackrill, John J.
• dc.contributor.author Wu, Yuanyuan
• dc.contributor.author Howard, Michael T.
• dc.contributor.author Capecchi, Mario
• dc.contributor.author Guigó Serra, Roderic
• dc.contributor.author Burk, Raymond F.
• dc.contributor.author Atkins, John F.
• dc.date.accessioned 2025-02-03T07:44:50Z
• dc.date.available 2025-02-03T07:44:50Z
• dc.date.issued 2016
• dc.description.abstract Dynamic 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.format.mimetype application/pdf
• dc.identifier.citation Wu S, Mariotti M, Santesmasses D, Hill KE, Baclaocos J, Aparicio-Prat E, et al. 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 Biol. 2016 Nov;6(11):160241. DOI: 10.1098/rsob.160241
• dc.identifier.doi http://dx.doi.org/10.1098/rsob.160241
• dc.identifier.issn 2046-2441
• dc.identifier.uri http://hdl.handle.net/10230/69437
• dc.language.iso eng
• dc.publisher Royal Society
• dc.relation.ispartof Open Biology. 2016 Nov;6(11):160241
• 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.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Codon redefinitionen
• dc.subject.keyword Ribosome specializationen
• dc.subject.keyword Selenocysteineen
• dc.subject.keyword Selenoprotein Pen
• dc.subject.keyword Selenoprotein Sen
• dc.title Human 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.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion