The Role of tRNA Modification Systemsin the Cellular StresstRNA修饰系统在细胞应激的作用.doc

The Role of tRNA Modification Systems in the Cellular Stress Response By Margaret Daly A Thesis Submitted to The University at Albany, State University of New York In Fulfillment of the Requirements for An Honors Biology Bachelor of Science Degree College of Arts and Science Department of Biology 2009 Abstract Background Transfer RNA(tRNA) is a small chain of nucleotides that participates in protein synthesis by pairing its anticodon with an mRNA codon and transferring an amino acid to a growing polypeptide chain. tRNA methyltransferases are a group of enzymes that can modify nucleosides in or around the anticodon, as well as at other parts of the tRNA. Recently, some of these modifications have been reported to enhance the translation of proteins that help the cell respond to and/or repair DNA damage. We hypothesize that the modifications catalyzed by some of the tRNA methyltransferases (Trms) stabilize the interaction between the mRNA codon and the tRNA anticodon thus enhancing the translation of transcripts with specific codon usage patterns. This enhanced translation may increase the levels of certain proteins necessary for the cell to respond to stress. Furthermore, we predict that their activity will dictate cellular responses to environmental carcinogens and chemotherapeutics. Results We exposed yeast gene deletion strains to carcinogens that cause cellular stress such as DNA damage, protein stress, and oxidative stress. Thus far, the effects of methyl methanesulfonate, tunicamycin, paramomycin, bleomycin, hygromycin, rapamycin, and hydrogen peroxide have been tested on 13 trm knockout strains. The results suggest that three of the tRNA methyltransferases may have a larger role in the stress response than the other ten trms. In particular, those tRNA methyltransferases that act to modify tRNA at the anticodon, or in close proximity to the anticodon, are the most important tRNA methyltransferases involved in stress responses. Trm4 and Trm5 seemed to