Talk abstracts
Talk on Friday 03:30-03:45pm submitted by Chenghong Deng
The Influence on Translation and Biological Affects by the tRNA Methytransferase 1 (TRMT1)
Chenghong Deng (University of Rochester), Dr. Kejia Zhang (University of Rochester), Xinyu Wang (University of Rochester), Grace Yang (University of Rochester), Helen Jackson, Jiaming Mao (University of Rochester), Dr. Dragony Fu (University of Rochester)
Abstract:
Pathogenic variants in the tRNA methyltransferase 1 (TRMT1) gene cause intellectual disability disorders in the human population. TRMT1 methylates a single guanine nucleotide in tRNAs to form the dimethylguanosine (m2,2G) modification. However, the specific role of TRMT1-catalyzed tRNA modifications in protein synthesis is unknown. To understand how TRMT1 affects tRNA function in translation, we performed ribosome profiling on wildtype and TRMT1-deficient human cells. We found that the majority of codons decoded by TRMT1-modified tRNAs showed increased ribosome occupancy in TRMT1-deficient samples. Moreover, we provide evidence that the increased ribosome occupancy on certain leucine codons is linked to reduced aminoacylation of leucine tRNA isoacceptors in TRMT1-deficient cells. Furthermore, we find that TRMT1-deficient cells exhibit reduced translation of leucine codon reporters. Consistent with ribosome stalling and collisions, we detect activation of the integrated stress response along with up-regulation of genes involved in apoptosis in TRMT1-deficient cell lines. Our results uncover specific roles for the m2,2G modification in tRNA stability and function that are important for ensuring proper translation and protein synthesis.
References:
Dewe, Joshua M., Benjamin L. Fuller, Jenna M. Lentini, Stefanie M. Kellner, and Dragony Fu. 2017. “TRMT1-Catalyzed TRNA Modifications Are Required for Redox Homeostasis To Ensure Proper Cellular Proliferation and Oxidative Stress Survival.” Molecular and Cellular Biology 37 (21): e00214-17. https://doi.org/10.1128/MCB.00214-17.
Zhang, Kejia, Jenna M Lentini, Christopher T Prevost, Mais O Hashem, Fowzan S Alkuraya, and Dragony Fu. 2019. “A Missense Variant Impairing TRMT1 Function in TRNA Modification Is Linked to Intellectual Disability.” Preprint. Molecular Biology. https://doi.org/10.1101/817247.
Keywords: tRNA Modification , Ribosome Profiling, Translation