Poster abstracts
Poster number 159 submitted by Aubree Zimmer
The basis of multi-step tRNA recognition by a eukaryotic tRNA editing deaminase
Luciano G. Dolce (European Molecular Biology Laboratory, Grenoble), Aubree A. Zimmer (Ohio State Biochemistry Program), Felix Weis (European Molecular Biology Laboratory, Heidelberg), Henry Arthur, Mary Anne T. Rubio, Katherine M. McKenney, Jessica L. Spears (Department of Microbiology, The Center for RNA Biology), Laura Tengo, Eva Kowalinksi (European Molecular Biology Laboratory, Grenoble), Juan D. Alfonzo (Department of Microbiology, The Center for RNA Biology)
Abstract:
Transfer RNAs (tRNAs) are central to protein synthesis by converting genomic information of protein-coding regions into a precise polypeptide chain, as dictated by codons in mRNA. tRNAs require extensive chemical modifications for structural stability, translation fidelity, as well as decoding functions. One such modification is the deamination of adenosine to inosine at the first position of the anticodon, which is essential for viability in bacteria and eukaryotes. Inosine formation at this wobble position in both bacteria and eukaryotes increases the decoding capabilities of a tRNA to recognize multiple different synonymous codons. The deaminase responsible for A-to-I activity in bacteria specifically deaminates a single tRNA while the eukaryotic counterpart has evolved to deaminate 7-8 tRNAs independent of any sequence specificity. How the eukaryotic enzyme recognizes multiple substrate tRNAs from non-substrate molecules has been a long-standing question in the field. In collaboration with the Kowalinski laboratory at the EMBL, we have described a model for tRNA recognition based on biochemical assays and the first structure of a eukaryotic deaminase bound to substrate tRNA. Our model describes a multi-step tRNA recognition mechanism using domains distal from the active site as well as an essential cation- π molecular gate guarding the catalytic site.
Keywords: tRNA editing, deaminase, Trypanosoma brucei