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Drug treatments and Diagnostic approaches: tRNA, tRFs and RNA modifications

Post-transcriptional RNA modifications play a pivotal role in governing mRNA translation and stability. In fact, recent strides in high-throughput RNA sequencing have unveiled a wide range of mRNA modifications that can influence mRNA degradation, targeting,  regulation, folding, splicing, and ribosome stalling. Such modifications are implicated in a wide range of diseases including cancer, neurological disorders, embryonic development disorders, and immune system dysfunction.  Understanding the intricate roles of RNA modifications is paramount for gaining deeper insights that may contribute to improving RNA-based drug treatments. 

Modifications on mRNA, tRNA, and tRNA fragments position these RNA species for great potential for use as diagnostic biomarkers, therapeutic targets, and innovative medicines. By targeting shared genetic mutations across multiple conditions, RNA/tRNA medicines may provide revolutionary new approaches to drug development for currently untreatable disorders.

As this field advances, continued exploration of RNA and tRNA biology, chemistry, and delivery is essential to fully unlock the potential of RNA and tRNA medicines and pave the way for their development into approved treatments. 

Immagina stands at the forefront of this endeavor, providing a comprehensive suite of solutions to enhance the understanding of how RNA modifications impact codon usage and translation. Our innovative nano-tRNAseq technology enables precise quantification of tRNA modifications and abundance. Our DOORs technology facilitates accurate quantification and omic profiling of tRNA fragments. 


It is the foundation of our initiative to commercialize a platform that will expand biomarker identification and drug development in new directions. Together, nano-tRNAseq and DOORs empower researchers with a multifaceted approach to unravel the intricacies of RNA dynamics and potential associations with development of disease and therapeutic response.

References

  • Anastassiadis, T. & Köhrer, C. Ushering in the era of tRNA medicines. Journal of Biological Chemistry 299, 105246 (2023).
  • Boo, S. H. & Kim, Y. K. The emerging role of RNA modifications in the regulation of mRNA stability. Exp Mol Med 52, 400–408 (2020).



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References and additional resources

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  9. Shu H, Donnard E, Liu B, Jung S, Wang R, Richter JD. FMRP links optimal codons to mRNA stability in neurons. Proc Natl Acad Sci U S A. 2020;117(48):30400-11.
  10. Martin S, Allan KC, Pinkard O, Sweet T, Tesar PJ, Coller J. Oligodendrocyte differentiation alters tRNA modifications and codon optimality-mediated mRNA decay. Nature Communications. 2022;13(1):5003.
  11. Jungfleisch J, Böttcher R, Talló-Parra M, Pérez-Vilaró G, Merits A, Novoa EM, et al. CHIKV infection reprograms codon optimality to favor viral RNA translation by altering the tRNA epitranscriptome. Nature Communications. 2022;13(1):4725. 
  12. https://www.science.org/doi/full/10.1126/sciadv.abj3967
  13. https://www.nature.com/articles/s41467-022-32791-2
  14. https://elifesciences.org/articles/52629
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