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

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dc.contributor.authorMariotti, Marco
dc.contributor.authorShetty, Sumangala
dc.contributor.authorBaird, Lisa
dc.contributor.authorWu, Sen
dc.contributor.authorLoughran, Gary
dc.contributor.authorCopeland, Paul R.
dc.contributor.authorAtkins, John F.
dc.contributor.authorHoward, Michael T.
dc.contributor.funderScience Foundation Ireland
dc.contributor.funderNational Institutes of Health
dc.date.accessioned2018-02-06T13:36:28Z
dc.date.available2018-02-06T13:36:28Z
dc.date.issued2017
dc.description.abstractGene-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.sponsorshipNational Institutes of Health (R37 ES02497; GM077073; R01 GM114291); Science Foundation Ireland (13/1A/1835)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationMariotti, 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/gkx982en
dc.identifier.doi10.1093/nar/gkx982
dc.identifier.endpage13015
dc.identifier.issn0305-1048
dc.identifier.issued22
dc.identifier.journaltitleNucleic Acids Researchen
dc.identifier.startpage13004
dc.identifier.urihttps://hdl.handle.net/10468/5387
dc.identifier.volume45
dc.language.isoenen
dc.publisherOxford University Pressen
dc.relation.urihttps://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.comen
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subjectUGA codonsen
dc.subjectRNA-protein complexesen
dc.subjectSelenoprotein Pen
dc.subjectmRNAen
dc.titleMultiple RNA structures affect translation initiation and UGA redefinition efficiency during synthesis of selenoprotein Pen
dc.typeArticle (peer-reviewed)en
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