Multiple RNA structures affect translation initiation and UGA redefinition efficiency during synthesis of selenoprotein P

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dc.contributor.author Mariotti, Marco
dc.contributor.author Shetty, Sumangala
dc.contributor.author Baird, Lisa
dc.contributor.author Wu, Sen
dc.contributor.author Loughran, Gary
dc.contributor.author Copeland, Paul R.
dc.contributor.author Atkins, John F.
dc.contributor.author Howard, Michael T.
dc.date.accessioned 2018-02-06T13:36:28Z
dc.date.available 2018-02-06T13:36:28Z
dc.date.issued 2017
dc.identifier.citation Mariotti, M., Shetty, S., Baird, L., Wu, S., Loughran, G., Copeland, P. R., Atkins, J. F. and Howard, M. T. (2017) 'Multiple RNA structures affect translation initiation and UGA redefinition efficiency during synthesis of selenoprotein P', Nucleic Acids Research, 45(22), pp. 13004-13015. doi: 10.1093/nar/gkx982 en
dc.identifier.volume 45
dc.identifier.issued 22
dc.identifier.startpage 13004
dc.identifier.endpage 13015
dc.identifier.issn 0305-1048
dc.identifier.uri http://hdl.handle.net/10468/5387
dc.identifier.doi 10.1093/nar/gkx982
dc.description.abstract Gene-specific expansion of the genetic code allows for UGA codons to specify the amino acid selenocysteine (Sec). A striking example of UGA redefinition occurs during translation of the mRNA coding for the selenium transport protein, selenoprotein P (SELENOP), which in vertebrates may contain up to 22 in-frame UGA codons. Sec incorporation at the first and downstream UGA codons occurs with variable efficiencies to control synthesis of full-length and truncated SELENOP isoforms. To address how the Selenop mRNA can direct dynamic codon redefinition in different regions of the same mRNA, we undertook a comprehensive search for phylogenetically conserved RNA structures and examined the function of these structures using cell-based assays, in vitro translation systems, and in vivo ribosome profiling of liver tissue from mice carrying genomic deletions of 3′ UTR selenocysteine-insertion-sequences (SECIS1 and SECIS2). The data support a novel RNA structure near the start codon that impacts translation initiation, structures located adjacent to UGA codons, additional coding sequence regions necessary for efficient production of full-length SELENOP, and distinct roles for SECIS1 and SECIS2 at UGA codons. Our results uncover a remarkable diversity of RNA elements conducting multiple occurrences of UGA redefinition to control the synthesis of full-length and truncated SELENOP isoforms. en
dc.description.sponsorship National Institutes of Health (R37 ES02497; GM077073; R01 GM114291); Science Foundation Ireland (13/1A/1835) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Oxford University Press en
dc.relation.uri https://academic.oup.com/nar/article/45/22/13004/4561653
dc.rights © 2017, the authors . Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com en
dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
dc.subject UGA codons en
dc.subject RNA-protein complexes en
dc.subject Selenoprotein P en
dc.subject mRNA en
dc.title Multiple RNA structures affect translation initiation and UGA redefinition efficiency during synthesis of selenoprotein P en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother j.atkins@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.internal.rssid 431799831
dc.contributor.funder Science Foundation Ireland
dc.contributor.funder National Institutes of Health
dc.description.status Peer reviewed en
dc.identifier.journaltitle Nucleic Acids Research en
dc.internal.IRISemailaddress John F. Atkins, Biochemistry, University College Cork , Cork, Ireland T: +353-21-490-3000. E: j.atkins@ucc.ie en


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© 2017, the authors . Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Except where otherwise noted, this item's license is described as © 2017, the authors . Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
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