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PMID: 11118223 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

SECIS-SBP2 interactions dictate selenocysteine incorporation efficiency and selenoprotein hierarchy.

The EMBO journal ·Vol. 19 ·No. 24 ·2000-12-15 ·Pages 6882-90

Low SC, Grundner-Culemann E, Harney JW, Berry MJ

Abstract

Selenocysteine incorporation at UGA codons requires cis-acting mRNA secondary structures and several specialized trans-acting factors. The latter include a selenocysteine-specific tRNA, an elongation factor specific for this tRNA and a SECIS-binding protein, SBP2, which recruits the elongation factor to the selenoprotein mRNA. Overexpression of selenoprotein mRNAs in transfected cells results in inefficient selenocysteine incorporation due to limitation of one or more of these factors. Using a transfection-based competition assay employing overexpression of selenoprotein mRNAs to compete for selenoprotein synthesis, we investigated the ability of the trans-acting factors to overcome competition and restore selenocysteine incorporation. We report that co-expression of SBP2 overcomes the limitation produced by selenoprotein mRNA overexpression, whereas selenocysteyl-tRNA and the selenocysteine-specific elongation factor do not. Competition studies indicate that once bound to SECIS elements, SBP2 does not readily exchange between them. Finally, we show that SBP2 preferentially stimulates incorporation directed by the seleno protein P and phospholipid hydroperoxide glutathione peroxidase SECIS elements over those of other selenoproteins. The mechanistic implications of these findings for the hierarchy of selenoprotein synthesis and nonsense-mediated decay are discussed.

MeSH Terms
Cell Line Genes, Reporter Humans Iodide Peroxidase/genetics,metabolism Mutagenesis, Site-Directed Open Reading Frames Protein Biosynthesis Proteins RNA, Messenger/genetics RNA-Binding Proteins/chemistry,genetics,metabolism Recombinant Proteins/chemistry,metabolism Selenocysteine/genetics,metabolism Selenoproteins Transcription, Genetic Transfection beta-Galactosidase/genetics,metabolism
Chemicals
Proteins RNA, Messenger RNA-Binding Proteins Recombinant Proteins SECISBP2 protein, human Selenoproteins Selenocysteine Iodide Peroxidase beta-Galactosidase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Low S C
Thyroid Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Grundner-Culemann E
Harney J W
Berry M J
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/19.24.6882
Published
2000-12-15
Pages
6882-90
Language
English
Region
England
NLM ID
8208664
PMCID
PMC305907
Subset
IM
Grants
NIDDK NIH HHS · R01 DK047320 · United States
NIDDK NIH HHS · DK-47320 · United States
NIDDK NIH HHS · R56 DK047320 · United States
NIDDK NIH HHS · DK-52963 · United States
NIDDK NIH HHS · R01 DK052963 · United States
External Links
PubMed source DOI: 10.1093/emboj/19.24.6882 PMC Full Text View journal details
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