Peer-Reviewed Journal Details
Mandatory Fields
Mariotti, M;Shetty, S;Baird, L;Wu, S;Loughran, G;Copeland, PR;Atkins, JF;Howard, MT
2017
December
Nucleic acids research
Multiple RNA structures affect translation initiation and UGA redefinition efficiency during synthesis of selenoprotein P
Validated
WOS: 13 ()
Optional Fields
OPEN READING FRAME 3 UNTRANSLATED REGION SELENOCYSTEINE INCORPORATION MESSENGER-RNA SELENIUM METABOLISM DECODING APPARATUS ELONGATION-FACTOR BINDING PROTEIN INSERTION CODONS
45
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.
OXFORD
0305-1048
10.1093/nar/gkx982
Grant Details