PUBLICATION
Processive incorporation of multiple selenocysteine residues is driven by a novel feature of the selenocysteine insertion sequence
- Authors
- Shetty, S.P., Sturts, R.J., Vetick, M.B., Copeland, P.R.
- ID
- ZDB-PUB-181017-5
- Date
- 2018
- Source
- The Journal of biological chemistry 293(50): 19377-19386 (Journal)
- Registered Authors
- Copeland, Paul
- Keywords
- 21st amino acid, RNA structure, mRNA, ribonuclear protein (RNP), selenium, selenocysteine, selenoprotein, stem loop structure
- MeSH Terms
-
- Base Sequence
- Conserved Sequence
- DNA Transposable Elements/genetics*
- HEK293 Cells
- Humans
- Selenocysteine*
- PubMed
- 30323062 Full text @ J. Biol. Chem.
Citation
Shetty, S.P., Sturts, R.J., Vetick, M.B., Copeland, P.R. (2018) Processive incorporation of multiple selenocysteine residues is driven by a novel feature of the selenocysteine insertion sequence. The Journal of biological chemistry. 293(50):19377-19386.
Abstract
RNA stem loop structures have been frequently shown to regulate essential cellular processes. The selenocysteine insertion sequence (SECIS) element, found in the 3' -UTRs of all selenoprotein mRNAs, is an example of such a structure, as it is required for the incorporation of the 21st amino acid, selenocysteine (Sec). Selenoprotein synthesis poses a mechanistic challenge since Sec is incorporated during translation in response to a stop codon (UGA). Although it is known that a SECIS-binding protein (SBP2) is required for Sec insertion, the mechanism of action remains elusive. Additional complexity is present in the synthesis of selenoprotein P (SELENOP), which is the only selenoprotein that contains multiple UGA codons and possesses two SECIS elements in its 3'-UTR. Thus, full-length SELENOP synthesis requires processive Sec incorporation. Using zebrafish Selenop, in vitro translation assays, and 75Se labeling in HEK293 cells, we found here that processive Sec incorporation is an intrinsic property of the SECIS elements. Specifically, we identified critical features of SECIS elements that are required for processive Sec incorporation. A screen of the human SECIS elements revealed that most of these elements support processive Sec incorporation in vitro; however, we also found that processivity of Sec incorporation into Selenop in cells is tightly regulated. We propose a model for processive Sec incorporation that involves differential recruitment of SECIS-binding proteins.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping