Transfer RNA anticodon loop modifications (tRNA modifications)

Transfer RNA (tRNA) anticodon loop modifications are chemical alterations, such as methylation, thiolation, and pseudouridylation, that occur primarily at the wobble position (U34) and position 37 of the tRNA molecule. These modifications are critical for maintaining the fidelity and efficiency of the translation process by stabilizing codon-anticodon interactions and preventing ribosomal frameshifting [1][2]. The enzymes responsible for these modifications, often referred to as tRNA-modifying enzymes or "writers," play a pivotal role in cellular adaptation to stress by regulating the translation of specific subsets of mRNAs [3]. Dysregulation of these modifications is a hallmark of several diseases, including various cancers where they support the translation of oncogenic drivers, and neurodegenerative disorders where their absence leads to protein misfolding [4][5]. Consequently, these modifications and their biosynthetic enzymes have emerged as promising therapeutic targets, particularly in oncology and infectious diseases [6]. Therapeutic strategies involve the development of small-molecule inhibitors to disrupt the translation of disease-relevant proteins or the use of modified nucleosides to restore normal tRNA function [7]. Sources: [1] Suzuki, T. (2021). Nature Reviews Molecular Cell Biology. [2] Agris, P. F., et al. (2007). RNA. [3] Chan, C. T., et al. (2012). Nature Communications. [4] Rapino, F., et al. (2018). Nature. [5] Wei, F. Y., et al. (2018). Journal of Clinical Investigation. [6] Begley, U., & Begley, T. J. (2021). Genes. [7] Delaunay, S., & Frye, M. (2019). Nature Cell Biology.

Other names

tRNA epitranscriptometRNA wobble modificationsAnticodon loop modificationstRNA-modifying enzymes

Inhibition of tRNA-modifying enzymes to disrupt the translation of specific codon-biased mRNAs and induce proteotoxic stress in target cells.