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Multiple RNA structures affect translation initiation and UGA redefinition efficiency during synthesis of selenoprotein P |
Mariotti, Marco; Shetty, Sumangala; Baird, Lisa; Wu, Sen; Loughran, Gary; Copeland, Paul R.; Atkins, John F.; Howard, Michael T.
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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.
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Keyword(s):
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UGA codons; RNA-protein complexes; Selenoprotein P; mRNA |
Publication Date:
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2017 |
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Type:
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Journal article |
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Peer-Reviewed:
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Yes |
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Language(s):
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English |
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Institution:
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University College Cork |
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Funder(s):
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Science Foundation Ireland |
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Citation(s):
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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 |
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Publisher(s):
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Oxford University Press |
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File Format(s):
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application/pdf |
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Related Link(s):
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https://academic.oup.com/nar/article/45/22/13004/4561653 |
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First Indexed:
2018-02-07 06:38:53 Last Updated:
2018-02-27 06:30:19 |
