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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.
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.
Keyword(s): UGA codons; RNA-protein complexes; Selenoprotein P; mRNA
Publication Date:
2017
Type: Journal article
Peer-Reviewed: Yes
Language(s): English
Institution: University College Cork
Funder(s): Science Foundation Ireland
Citation(s): 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
Publisher(s): Oxford University Press
File Format(s): application/pdf
Related Link(s): https://academic.oup.com/nar/article/45/22/13004/4561653
First Indexed: 2018-02-07 06:38:53 Last Updated: 2018-02-27 06:30:19