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SBP2 binding affinity is a major determinant in differential selenoprotein mRNA translation and sensitivity to nonsense‐mediated decay
Author(s) -
Squires Jeffrey E
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.696.7
Subject(s) - selenoprotein , selenocysteine , nucleolin , messenger rna , biology , nonsense mediated decay , stop codon , translation (biology) , microbiology and biotechnology , rna , biochemistry , gene , cysteine , nucleolus , cytoplasm , rna splicing , glutathione , glutathione peroxidase , enzyme
Selenoprotein mRNAs are potential targets for degradation via nonsense‐mediated decay due to the presence of in‐frame UGA codons that can be decoded as either selenocysteine or termination codons. When UGA decoding is inefficient, as occurs when selenium is limiting, termination occurs at these positions. Based on predicted exon‐intron structure, fourteen of the 25 human selenoprotein mRNAs are predicted to be sensitive to nonsense‐mediated decay. Among these, sensitivity varies widely, resulting in a hierarchy of preservation or degradation of selenoprotein mRNAs and thus, of selenoprotein synthesis. Potential factors dictating the hierarchy of selenoprotein synthesis are the SECIS RNA‐binding proteins, SBP2 and nucleolin. To investigate the mechanistic basis for this hierarchy and the role of these two proteins, we carried out knockdowns of SBP2 expression and analyzed the effects on selenoprotein mRNA levels. We also investigated in vivo binding of selenoprotein mRNAs by SBP2 and nucleolin, via immunoprecipitation of the proteins and quantitation of bound mRNAs. We report that SBP2 exhibits strong preferential binding to some selenoprotein mRNAs over others, whereas nucleolin exhibits minimal differences in binding. Thus, SBP2 is a major determinant in dictating the hierarchy of selenoprotein synthesis via differential selenoprotein mRNA translation and sensitivity to nonsense‐mediated decay.