PUBLICATION
The Selenium Transport Protein, Selenoprotein P, Requires Coding Sequence Determinants to Promote Efficient Selenocysteine Incorporation
- Authors
- Shetty, S.P., Copeland, P.R.
- ID
- ZDB-PUB-190928-11
- Date
- 2018
- Source
- Journal of molecular biology 430: 5217-5232 (Journal)
- Registered Authors
- Copeland, Paul
- Keywords
- SELENOP, efficiency, processivity, selenocysteine, selenoprotein
- MeSH Terms
-
- 3' Untranslated Regions
- Animals
- Codon, Terminator
- HEK293 Cells
- Humans
- Nucleic Acid Conformation
- Protein Biosynthesis
- RNA, Messenger/chemistry*
- Selenocysteine/metabolism*
- Selenoprotein P/chemistry
- Selenoprotein P/genetics
- Selenoprotein P/metabolism*
- Selenoproteins/chemistry
- Selenoproteins/genetics
- Selenoproteins/metabolism*
- Zebrafish
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 30243837 Full text @ J. Mol. Biol.
Citation
Shetty, S.P., Copeland, P.R. (2018) The Selenium Transport Protein, Selenoprotein P, Requires Coding Sequence Determinants to Promote Efficient Selenocysteine Incorporation. Journal of molecular biology. 430:5217-5232.
Abstract
Selenoproteins are an essential and unique group of proteins in which selenocysteine (Sec) is incorporated in response to a stop codon (UGA). Reprograming of UGA for Sec insertion in eukaryotes requires a cis-acting stem-loop structure in the 3' untranslated region of selenoprotein mRNA and several trans-acting factors. Together these factors are sufficient for Sec incorporation in vitro, but the process is highly inefficient. An additional challenge is the synthesis of selenoprotein P (SELENOP), which uniquely contains multiple UGA codons. Full-length SELENOP expression requires processive Sec incorporation, the mechanism for which is not understood. In this study, we identify core coding region sequence determinants within the SELENOP mRNA that govern SELENOP synthesis. Using 75Se labeling in cells, we determined that the N-terminal coding sequence (upstream of the second UGA) and C-terminal coding sequence context are two independent determinants for efficient synthesis of full-length SELENOP. In addition, the distance between the first UGA and the consensus signal peptide is also critical for efficiency.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping