PUBLICATION
Efficient incorporation of multiple selenocysteines involves an inefficient decoding step serving as a potential translational checkpoint and ribosome bottleneck
- Authors
- Stoytcheva, Z., Tujebajeva, R.M., Harney, J.W., and Berry, M.J.
- ID
- ZDB-PUB-080602-2
- Date
- 2006
- Source
- Molecular and cellular biology 26(24): 9177-9184 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Selenocysteine/genetics
- Selenocysteine/metabolism*
- RNA Precursors/biosynthesis
- RNA Precursors/genetics
- RNA Precursors/metabolism
- Evolution, Molecular
- Humans
- Cell Line
- Zebrafish
- Codon/genetics*
- Ribosomes/genetics*
- Selenoprotein P/biosynthesis
- Selenoprotein P/genetics*
- Selenoprotein P/metabolism
- Codon, Terminator/genetics
- Zebrafish Proteins/biosynthesis
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- Sequence Deletion
- Protein Biosynthesis*/genetics
- Mutation
- Animals
- PubMed
- 17000762 Full text @ Mol. Cell. Biol.
Citation
Stoytcheva, Z., Tujebajeva, R.M., Harney, J.W., and Berry, M.J. (2006) Efficient incorporation of multiple selenocysteines involves an inefficient decoding step serving as a potential translational checkpoint and ribosome bottleneck. Molecular and cellular biology. 26(24):9177-9184.
Abstract
Selenocysteine is incorporated into proteins via "recoding" of UGA from a stop codon to a sense codon, a process that requires specific secondary structures in the 3' untranslated region, termed selenocysteine incorporation sequence (SECIS) elements, and the protein factors that they recruit. Whereas most selenoprotein mRNAs contain a single UGA codon and a single SECIS element, selenoprotein P genes encode multiple UGAs and two SECIS elements. We have identified evolutionary adaptations in selenoprotein P genes that contribute to the efficiency of incorporating multiple selenocysteine residues in this protein. The first is a conserved, inefficiently decoded UGA codon in the N-terminal region, which appears to serve both as a checkpoint for the presence of factors required for selenocysteine incorporation and as a "bottleneck," slowing down the progress of elongating ribosomes. The second adaptation involves the presence of introns downstream of this inefficiently decoded UGA which confer the potential for nonsense-mediated decay when factors required for selenocysteine incorporation are limiting. Third, the two SECIS elements in selenoprotein P mRNA function with differing efficiencies, affecting both the rate and the efficiency of decoding different UGAs. The implications for how these factors contribute to the decoding of multiple selenocysteine residues are discussed.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping