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Identification of selenoproteins exhibiting resistance to nonsense‐mediated decay under selenium deficiency
Author(s) -
Seyedali Ali,
Gilman Christy L,
Seale Lucia A,
Berry Marla J
Publication year - 2010
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.24.1_supplement.218.2
Subject(s) - selenoprotein , selenocysteine , nonsense mediated decay , translation (biology) , selenoprotein p , biology , alternative splicing , stop codon , exon , rna splicing , protein biosynthesis , messenger rna , microbiology and biotechnology , genetics , chemistry , amino acid , biochemistry , gene , rna , enzyme , cysteine , glutathione , glutathione peroxidase
Selenoproteins, defined by the presence of the 21 st amino acid selenocysteine (Sec), exhibit functions vital to cellular well‐being. Sec translation into protein occurs via the stop codon UGA and requires recoding by means of secondary structures in the 3′UTR associating with trans‐acting factors. This Sec‐specific UGA creates competition between selenoprotein biosynthesis and the nonsense‐mediated decay pathway (NMD); a pathway functioning to protect the cell from bulk translation of potentially deleterious truncated proteins. A recent study reported that eIF4a3, a protein component of the exon junction complexes deposited near exon junctions during splicing, binds the SECIS elements of select selenoprotein mRNAs under selenium deficiency and prevents Sec incorporation into protein. This translational inhibition does not necessarily increase NMD. Characterization of selenoprotein mRNAs reveal insights into NMD resistance. Several studies have identified variability in selenoprotein mRNA and protein levels under selenium deficiency. Our aim was to characterize expression of selenoproteins and their mRNAs under selenium deficiency and to elucidate underlying mechanisms. We have found that selenoproteins exhibit a wide variety of tissue specific dependence on selenium supply and that overexpression of eIF4a3 in HEK293 cells resulted in a decrease in certain selenoprotein mRNAs.