Aminoacyl-tRNA Synthesis by Pre-translational Amino Acid Modification

Yale University, New Haven CT

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Abstract

DESCRIPTION (provided by applicant): Biogenesis of small noncoding RNAs is essential for proper cell functioning. The many steps of small RNA biogenesis must each be successfully completed to produce a mature RNA that is able to perform its particular cellular function. Mistakes at any step can result in accumulation of aberrant RNAs and have deleterious consequences for the cell. Therefore, the ability to survey RNA, ensuring accuracy at each step of biogenesis, and eliminate aberrant RNA is necessary for normal cell functioning. The experiments proposed here should give insights into the poorly understood process by which defective, noncoding RNAs are recognized and targeted for destruction. Trf4p was recently shown to function in targeting a mutant tRNA for degradation via polyadenylation and subsequent degradation by the exosome in yeast; we will determine whether Trf4p has a general function in the quality control of small noncoding RNAs. Additionally, our data indicates an interaction between the La protein, the first protein to bind nascent RNA polymerase III transcripts, and Trf4p; we will examine the role of the La protein in small RNA quality control. Lastly, we will also examine the quality control pathway of another mutant tRNA that differs from the Trf4p-initiated pathway.