Inhibition of the aminoacylation of selected tRNA molecules by an estrogen-regulated factor on uterine ribosomes. Regulation of aminoacylation of tRNA by estrogens.
Administration of estradiol to ovariectomized mature rats for 1 h induces a transient increase in the peptide elongation rate on uterine ribosomes. An inhibitor of the peptide elongation rate, which appears to be regulated by estrogen treatment in vivo, can be extracted from ribosomes of estrogen-deprived rats. The extracted inhibitor or a native inhibitor-ribosome complex affects the rate of the peptide elongation reaction in a uterine cell-free protein synthesis system by inhibiting the ability of selected tRNAs in the assay to be charged with amino acids by their respective aminoacyl-tRNA synthetases. The degree of inhibition of charging of the affected tRNAs ranges from 22% to 78%, the order of inhibition being Pro greater than Val greater than Arg greater than Try greater than Leu greater than Glu greater than Ile greater than Gly greater than His greater than Ser greater than Lys. Inhibition results from a specific dose-dependent, and presumably reversible, effect of the inhibitor on tRNA, but not on the aminoacyl-tRNA synthetase. The effect does not result from removal of A-C-C terminal nucleotides from the 3' end of tRNA, but does inhibit the ability of selected tRNAs to bind to the aminoacyl-tRNA synthetases. We propose that regulation of the peptide elongation rate on uterine ribosomes by estradiol occurs through the estradiol-induced inactivation of a ribosome-associated inhibitor, which causes a reversible alteration to selected tRNAs. The modified tRNAs are unable to bind to their respective aminoacyl-tRNA synthetase to become charged with an amino acid thus causing the availability of selected aminoacyl-tRNAs to become rate-limiting in the sequential elongation of peptides.
D000604:Amino Acyl-tRNA Synthetases / Q000037:antagonists & inhibitors* / Q000502:physiology; D000818:Animals; D002474:Cell-Free System; D055598:Chemical Phenomena; D002621:Chemistry; D004958:Estradiol / Q000502:physiology*; D005260:Female; D010445:Peptide Elongation Factors / Q000302:isolation & purification / Q000378:metabolism; D011485:Protein Binding; D012343:RNA, Transfer / Q000378:metabolism*; D051381:Rats; D012270:Ribosomes / Q000378:metabolism*; D014599:Uterus / Q000378:metabolism*
D010445:Peptide Elongation Factors; D004958:Estradiol; D012343:RNA, Transfer; D000604:Amino Acyl-tRNA Synthetases