Transfer RNA modification and infection – Implications for pathogenicity and host responses

Transfer RNA (tRNA) molecules are sumptuously decorated with evolutionary conserved post-transcriptional nucleoside modifications that are essential for structural stability and ensure efficient protein translation. The tRNA modification levels change significantly in response to physiological stresses, altering translation in a number of ways. For instance, tRNA hypomodification leads to translational slowdown, disrupting protein homeostasis and reducing cellular fitness. This highlights the importance of proper tRNA modification as a determinant for maintaining cellular function and viability during stress. Furthermore, the expression of several microbial virulence factors is induced by changes in environmental conditions; a process where tRNA 2-thiolation is unequivocal for pathogenicity. In this review, we discuss the multifaceted implications of tRNA modification for infection by examining the roles of nucleoside modification in tRNA biology. Future development of novel methods and combinatory utilization of existing technologies will bring tRNA modification-mediated regulation of cellular immunity and pathogenicity to the limelight. •Post-transcriptional tRNA modifications are indispensable for efficient protein synthesis.•tRNA modifications alter genome structure, codon usage and translational fidelity.•tRNA wobble modifications regulate cellular protein homeostasis and cell viability.•2-thiolation is essential for microbial pathogenicity.•The dynamics of tRNA modification contribute to the virulence of pathogens.