Processive recoding and metazoan evolution of selenoprotein P: Up to 132 UGAs in molluscs

dc.contributor.authorBaclaocos, Janinah
dc.contributor.authorSantesmasses, Didac
dc.contributor.authorMariotti, Marco
dc.contributor.authorBierła, Katarzyna
dc.contributor.authorVetick, Michael B.
dc.contributor.authorLynch, Sharon
dc.contributor.authorMcAllen, Rob
dc.contributor.authorMackrill, John J.
dc.contributor.authorLoughran, Gary
dc.contributor.authorGuigó, Roderic
dc.contributor.authorSzpunar, Joanna
dc.contributor.authorCopeland, Paul R.
dc.contributor.authorGladyshev, Vadim N.
dc.contributor.authorAtkins, John F.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderIrish Research Councilen
dc.contributor.funderSpanish Ministry of Economy and Competitivenessen
dc.contributor.funderEMBOen
dc.contributor.funderNational Institutes of Healthen
dc.date.accessioned2019-10-15T05:59:08Z
dc.date.available2019-10-15T05:59:08Z
dc.date.issued2019-08-20
dc.description.abstractSelenoproteins typically contain a single selenocysteine, the 21st amino acid, encoded by a context-redefined UGA. However, human selenoprotein P (SelenoP) has a redox-functioning selenocysteine in its N-terminal domain and nine selenium transporter-functioning selenocysteines in its C-terminal domain. Here we show that diverse SelenoP genes are present across metazoa with highly variable numbers of Sec-UGAs, ranging from a single UGA in certain insects, to 9 in common spider, and up to 132 in bivalve molluscs. SelenoP genes were shaped by a dynamic evolutionary process linked to selenium usage. Gene evolution featured modular expansions of an ancestral multi-Sec domain, which led to particularly Sec-rich SelenoP proteins in many aquatic organisms. We focused on molluscs, and chose Pacific oyster Magallana gigas as experimental model. We show that oyster SelenoP mRNA with 46 UGAs is translated full-length in vivo. Ribosome profiling indicates that selenocysteine specification occurs with ~5% efficiency at UGA1 and approaches 100% efficiency at distal 3′ UGAs. We report genetic elements relevant to its expression, including a leader open reading frame and an RNA structure overlapping the initiation codon that modulates ribosome progression in a selenium-dependent manner. Unlike their mammalian counterparts, the two SECIS elements in oyster SelenoP (3′UTR recoding elements) do not show functional differentiation in vitro. Oysters can increase their tissue selenium level up to 50-fold upon supplementation, which also results in extensive changes in selenoprotein expression.en
dc.description.sponsorshipSpanish Ministry of Economy and Competitiveness ( BIO2014-57291-R); Irish Research Council (IRCLA/2019/74 n); EMBO short-term fellowship (ASTF 289-2014); National Institutes of Health ( DK117149, GM065204, AG021518, and GM077073)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationBaclaocos, J., Santesmasses, D., Mariotti, M., Bierła, K., Vetick, M. B., Lynch, S., McAllen, R., Mackrill, J. J., Loughran, G., Guigó, R., Szpunar, J., Copeland, P. R., Gladyshev, V. N. and Atkins, J. F. (2019) 'Processive Recoding and Metazoan Evolution of Selenoprotein P: Up to 132 UGAs in Molluscs', Journal of Molecular Biology.,(27pp.) [In press] DOI: 10.1016/j.jmb.2019.08.007en
dc.identifier.doi10.1016/j.jmb.2019.08.007en
dc.identifier.eissn1089-8638
dc.identifier.endpage27en
dc.identifier.issn0022-2836
dc.identifier.journaltitleJournal of Molecular Biologyen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/8769
dc.language.isoenen
dc.publisherAcademic Pressen
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.urihttps://www.sciencedirect.com/science/article/pii/S0022283619305133?via%3Dihub
dc.rights©2019 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/)en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectSelenoproteinen
dc.subjectSelenocysteineen
dc.subjectRecodingen
dc.subjectDynamic redefinitionen
dc.subjectEvolutionen
dc.titleProcessive recoding and metazoan evolution of selenoprotein P: Up to 132 UGAs in molluscsen
dc.typeArticle (peer-reviewed)en
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