9513127 Goldman This research will address the question of what happens at a "hungry codon" with limiting charged cognate tRNA. The main hypothesis to be tested is that premature termination of translation occurs at the hungry codon possibly generating, in some instances, functional products. A combination of genetic and biochemical approaches utilizing mutant alleles, along with cloned, regulatable genes, will be employed for in vivo experiments. A key goal will be to isolate truncated MS2 coat protein in pth mutants which have mutant Trp-tRNA (with higher Km). Factors governing the accuracy and efficiency of translation are of fundamental importance, with implications for understanding various diseases, differentiation, mechanisms of aging, as well as implications for genetic engineering. This research will contribute to understanding how tRNA molecules influence efficiency, accuracy, and regulation of translation. %%% The accurate transfer of genetic information in cells heavily relies upon the faithful translation of mRNA (which reflects the genetic coding for proteins) by transfer RNA (tRNA) molecules which serve as the interface between the genetic code and protein synthesis. It is now apparent that the molecular rules governing decoding of mRNA by tRNA are complicated and determined in part by cellular conditions. This research will explore what happens under conditions in which the appropriate amino acid-bound tRNA (charged cognate tRNA) is limiting. The hypothesis to be tested is that this condition leads to premature termination of synthesis at the "hungry codon", giving rise to truncated proteins. Factors governing protein synthesis are of fundamental importance, with implications for understanding various diseases, differentiation, perhaps aging, as well as for genetic engineering. The experiments to be conducted will contribute to our understanding of the efficiency, accuracy, and regulation of protein synthesis, and how tRNA molecules influence this processes. *** ??
