Inhibition of protein synthesis in rabbit reticulocyte lysates by double-stranded RNA and oxidized glutathione: indirect mode of action on polypeptide chain initiation.
In the presence of added double-stranded RNA or oxidized glutathione, protein synthesis in heminsupplemented reticulocyte lysates declines abruptly after 8-12 min of incubation at 30 degrees. The kinetics of amino-acid incorporation are very similar to those seen when lysates incorporation are very similar to those seen when lysates are incubated in the absence of added hemin. The inhibitory effects of double-stranded RNA (dsRNA) and oxidized glutathione (GSSG) are partially overcome by a homogeneous initiation factor, IF-MP, which also stimulates protein synthesis in hemin-deficient lysates. This factor is involved in the binding of Met-tRNAfmet to 40S ribosomal subunits during protein chain initiation. However, neither dsRNA alone nor GSSG alone significantly inhibits formation of [40S subunit-Met-tRNAf] complexes induced in reticulocyte lysates by dsRNA or GSSG involves one or more components present in the lysates but absent from the fractionated in vitro system. Such components may be related to the translational inhibitor that is active in hemin-deficient lysates.
D000818:Animals; D001665:Binding Sites; D001798:Blood Proteins / Q000096:biosynthesis*; D005978:Glutathione / Q000494:pharmacology*; D006427:Hemin / Q000494:pharmacology; D008715:Methionine; D010084:Oxidation-Reduction; D010408:Penicillium chrysogenum; D010442:Peptide Chain Initiation, Translational / Q000187:drug effects; D010448:Peptide Initiation Factors; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000187:drug effects*; D012313:RNA / Q000494:pharmacology*; D012343:RNA, Transfer / Q000378:metabolism; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D013997:Time Factors
D001798:Blood Proteins; D010448:Peptide Initiation Factors; D012313:RNA; D006427:Hemin; D012343:RNA, Transfer; D008715:Methionine; D005978:Glutathione