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

Show simple item record

dc.contributor.author Wu, Sen
dc.contributor.author Mariotti, Marco
dc.contributor.author Santesmasses, Didac
dc.contributor.author Hill, Kristina E.
dc.contributor.author Baclaocos, Janinah
dc.contributor.author Aparicio-Prat, Estel
dc.contributor.author Li, Shuping
dc.contributor.author Mackrill, John
dc.contributor.author Wu, Yuanyuan
dc.contributor.author Howard, Michael T.
dc.contributor.author Capecchi, Mario
dc.contributor.author Guigó, Roderic
dc.contributor.author Burk, Raymond F.
dc.contributor.author Atkins, John F.
dc.date.accessioned 2018-03-28T14:55:57Z
dc.date.available 2018-03-28T14:55:57Z
dc.date.issued 2016-11-23
dc.identifier.citation Wu, 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.160241 en
dc.identifier.volume 6 en
dc.identifier.issued 11 en
dc.identifier.startpage 160241-1 en
dc.identifier.endpage 160241-16 en
dc.identifier.issn 2046-2441
dc.identifier.uri http://hdl.handle.net/10468/5714
dc.identifier.doi 10.1098/rsob.160241
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.description.sponsorship Ministry 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.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher The Royal Society en
dc.relation.uri http://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.uri http://creativecommons.org/licenses/by/4.0/ en
dc.subject Codon redefinition en
dc.subject Ribosome specialization en
dc.subject Selenocysteine en
dc.subject Selenoprotein P en
dc.subject Selenoprotein S en
dc.subject Genetics en
dc.subject Molecular biology en
dc.subject Cellular biology en
dc.subject Bioinformatics en
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 elements en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother John F. Atkins, Biochemistry, University College Cork, Cork, Ireland. +353-21-490-3000 Email: j.atkins@ucc.ie en
dc.internal.availability Full text available en
dc.date.updated 2018-03-28T14:44:54Z
dc.description.version Published Version en
dc.internal.rssid 431673411
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Ministry of Agriculture of the People's Republic of China en
dc.contributor.funder National Institutes of Health en
dc.contributor.funder Howard Hughes Medical Institute en
dc.contributor.funder EMBO en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Open Biology en
dc.internal.copyrightchecked No !!CORA!! en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress j.atkins@ucc.ie en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Investigator Programme/13/IA/1853/IE/Dynamic redefinition of codons: From antivirals to an essential micronutrient/ en


Files in this item

This item appears in the following Collection(s)

Show simple item record

© 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. Except where otherwise noted, this item's license is described as © 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.
This website uses cookies. By using this website, you consent to the use of cookies in accordance with the UCC Privacy and Cookies Statement. For more information about cookies and how you can disable them, visit our Privacy and Cookies statement