Poster abstracts
Poster number 167 submitted by Kejia Zhang
Deciphering the biological function of tRNA methyltransferase 1 (TRMT1) using mouse models
Kejia Zhang (Department of Biology, Center for RNA Biology, University of Rochester), Prevost, Christopher (Department of Biology, Center for RNA Biology, University of Rochester), Fu, Dragony (Department of Biology, Center for RNA Biology, University of Rochester)
Abstract:
In all organisms, transfer RNAs (tRNA) undergo a series of post-transcriptional modifications by enzymes. One of the first discovered tRNA modification enzymes is tRNA methyltransferase 1(TRMT1), who catalyzes the formation of the dimethylguanosine (m2,2G) in numerous tRNAs. Mutations in the TRMT1 gene are the cause of autosomal-recessive intellectual disability (ARID) in the human population. However, the link between TRMT1 and neurodevelopment is still unclear. To understand the biological function of TRMT1 in mammals, we analyzed the functional consequences and phenotype by using TRMT1 knockout mice. We are able to knockout the expression of TRMT1 in all the organs and observe the loss of tRNA m2,2G modification. We observe that the TRMT1 KO mice exhibit the reduced body weight postweaning, smaller brain size and abnormal grip strength. Notably, we find that TRMT1 exhibits ubiquitous expression in the brain with enrichment in the hippocampus and neocortex. Moreover, compared to the wildtype mice, the TRMT1 KO mice show significantly reduced learning and spatial memory in Repeated Acquisition and Performance Chamber (RAPC) test. These results indicate that TRMT1 exhibits expression in brain areas associated with learning and memory, and TRMT1 plays a role in maintaining normal brain morphology and function during development, which is coincident with the syndrome observed in the patients. In the future, we plan to use neuronal staining and immunofluorescence to check the morphological changes of dendrites and molecular pathway affected by TRMT1.
References:
Dewe JM, Fuller BL, Lentini JM, Kellner SM, Fu D. TRMT1-catalyzed tRNA modifications are required for redox homeostasis to ensure proper cellular proliferation and oxidative stress survival. Molecular and Cellular Biology. 2017;37(21).
Davarniya B, Hu H, Kahrizi K, Musante L, Fattahi Z, Hosseini M, et al. The role of a novel TRMT1 gene mutation and rare GRM1 gene defect in intellectual disability in two azeri families. PLoS ONE. 2015;10(8):e0129631-.
Keywords: tRNA modification, TRMT1