Poster abstracts
Poster number 19 submitted by Nathan Howell
Distinct substrate specificities of human tRNA methyltransferases TRMT10A and TRMT10B
Nathan Howell (Ohio State University), Jane Jackman (Ohio State University)
Abstract:
Substantial biological resources are invested into producing functional tRNA molecules, including an extensive system of post-transcriptional nucleotide modifications. In this universal process, chemical functional groups are changed, rearranged, and added to individual nucleotides in a specific pattern for each target tRNA. One such modification is the addition of a methyl group to the N-1 atom of ninth-position purines (m1N9), which occurs in archaea and eukarya and is catalyzed by the Trm10 family of enzymes. We sought to explain the unusual presence of two predicted cytosolic Trm10 homologs (TRMT10A and TRMT10B) in humans and other metazoa. A yeast genetic system established in our lab suggested that TRMT10A and TRMT10B are not functionally redundant, leading to the use of in vitro approaches to investigate the substrate specificities of each enzyme. Using a combination of kinetic and binding assays, we demonstrate that human TRMT10A and TRMT10B exhibit distinct tRNA substrate specificities that are consistent with known modification patterns in human tRNA. Ongoing experiments suggest a new model for control of Trm10 substrate recognition based on interactions between Trm10 and other tRNA modification enzymes, which had not been previously observed for this enzyme family and has important implications for the behavior of Trm10 enzymes in diverse biological systems.
Keywords: tRNA modifications, enzymology, Trm10