Poster number 124 submitted by Chenghong Deng
The influence on transcription and translation by the TRMT1 tRNA modification enzyme
Chenghong Deng (Biology, University of Rochester), Kejia Zhang (Biology, University of Rochester), Dragony Fu (Biology, University of Rochester)
A series of post-transcriptional modifications are placed on transfer RNAs (tRNA) in all organisms. As one example, tRNA methyltransferase 1 (TRMT1) is a tRNA modifying enzyme which methylates a guanine residue at position 26 to form dimethylguanosine (m2,2G). Pathogenic variants in TRMT1 cause intellectual disability disorders in the human population. However, the link between TRMT1 and gene expression is unknown. To understand how TRMT1 affects gene expression and protein translation, we performed transcriptomics and ribosome profiling on wild-type or TRMT1-deficient human cells. At the transcriptional level, we identified a gene called BASP1 that is upregulated by 2-fold in TRMT1-deficient human cells. BASP1 encodes a brain-abundant membrane-attached signal protein. By upregulation of BASP1, the signal transmission will also be upregulated in TRMT1 – deficient cells. The results indicate that TRMT1 is important for maintaining the expression level for a subset of genes. In the future, we plan to use a TRMT1-deficient mouse model to further investigate the genes and pathways linked to TRMT1 in human cells.
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, TRMT1