Poster abstracts
Poster number 19 submitted by Yu Hsun Huang
Investigating Potential Roles of tRNA-Arg-TCT-2-1 in Regulation of Hes7 and Embryonic Laterality
Yu Hsun Huang (Department of Molecular Genetics, The Ohio State University), Moulisubhro Datta (Department of Chemistry and Biochemistry, The Ohio State University), Lillian Wooden (Department of Molecular Genetics, The Ohio State University), Venkat Gopalan (Department of Chemistry and Biochemistry, The Ohio State University), Susan E. Cole (Department of Molecular Genetics, The Ohio State University)
Abstract:
Transfer RNAs play an important role in protein synthesis, but growing evidence suggests that tRNA isodecoders may have regulatory roles beyond their canonical function. Hes7 is a key developmental gene involved in Somitogenesis. We have identified a conserved tRNA-Arg-TCT-2-1 sequence embedded within the Hes7 3’ UTR. We first investigated whether this element could influence Hes7 gene expression. We found that disruption of tRNA expression increases reporter protein levels without significantly affecting mRNA abundance, suggesting a potential role in Hes7 translation. In parallel, a rare human single-nucleotide variant (SNP) within tRNA-Arg-TCT-2-1 has been identified in a patient with a laterality defect, raising the question of whether this tRNA has specific developmental functions. Our analysis suggests that this variant disrupts a putative RNA polymerase III termination signal and indicates increased accumulation of unprocessed tRNA species. To investigate the role of this tRNA in laterality development, we generated tRNA-Arg-TCT-2-1 mutant mouse lines. Together, these findings support tRNA-Arg-TCT-2-1 may have multiple non-canonical roles: influencing expression of Hes7, and perhaps regulating left right patterning
References:
Söll, D. (2020). Naturally occurring trnas with non-canonical structures. Frontiers in Microbiology, 11. https://doi.org/10.3389/fmicb.2020.596914 Kapur M, Ganguly A, Nagy G, Adamson SI, Chuang JH, Frankel WN, Ackerman SL. Expression of the Neuronal tRNA n-Tr20 Regulates Synaptic Transmission and Seizure Susceptibility. Neuron. 2020 Oct 14;108(1):193-208.e9. doi: 10.1016/j.neuron.2020.07.023. Epub 2020 Aug 26. PMID: 32853550; PMCID: PMC7572898.
Netravathi, M., Kumari, R., Kapoor, S. et al. Whole exome sequencing in an Indian family links Coats plus syndrome and dextrocardia with a homozygous novel CTC1 and a rare HES7 variation. BMC Medical
Genetics 16, 5 (2015). https://doi.org/10.1186/s12881-015-0151-8
Keywords: tRNA, Laterality development, Hes7