| First Author | Mariotti M | Year | 2017 |
| Journal | Nucleic Acids Res | Volume | 45 |
| Issue | 22 | Pages | 13004-13015 |
| PubMed ID | 29069514 | Mgi Jnum | J:254688 |
| Mgi Id | MGI:6103346 | Doi | 10.1093/nar/gkx982 |
| Citation | Mariotti M, et al. (2017) Multiple RNA structures affect translation initiation and UGA redefinition efficiency during synthesis of selenoprotein P. Nucleic Acids Res 45(22):13004-13015 |
| abstractText | 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. |
