The tRNA identity landscape for aminoacylation and beyond

Abstract

tRNAs are key partners in ribosome-dependent protein synthesis. This process is highly dependent on the fidelity of tRNA aminoacylation by aminoacyl-tRNA synthetases and relies primarily on sets of identities within tRNA molecules composed of determinants and antideterminants preventing mischarging by non-cognate synthetases. Such identity sets were discovered in the tRNAs of a few model organisms, and their properties were generalized as universal identity rules. Since then, the panel of identity elements governing the accuracy of tRNA aminoacylation has expanded considerably, but the increasing number of reported functional idiosyncrasies has led to some confusion. In parallel, the description of other processes involving tRNAs, often well beyond aminoacylation, has progressed considerably, greatly expanding their interactome and uncovering multiple novel identities on the same tRNA molecule. This review highlights key findings on the mechanistics and evolution of tRNA and tRNA-like identities. In addition, new methods and their results for searching sets of multiple identities on a single tRNA are discussed. Taken together, this knowledge shows that a comprehensive understanding of the functional role of individual and collective nucleotide identity sets in tRNA molecules is needed for medical, biotechnological and other applications.

A tRNA modification inMycobacterium tuberculosisfacilitates optimal intracellular growth

“…This modification enhances the stacking of s 2 U with U35 to stabilize the anticodon structure, facilitating codon-anticodon interactions. s 2 U is also recognized by multiple aminoacyl-tRNA synthetases for efficient amino acylation[12]. Although elimination of this sulfur modification causes severe growth phenotypes in most organisms[39, 49], unexpectedly, the deletion of mnmA in Mtb did not attenuate growth of the pathogen in vitro , suggesting that the Mtb requirement for s 2 U modification differs from other organisms.…”

“…Chemical modifications of tRNA (tRNA modifications) are found in all kingdoms of life and fine-tune tRNA properties including mRNA decoding efficiency, recognition by aminoacyl-tRNA synthetases, half-life and structural stability [2,[10][11][12]. Modifications are prevalent in the anticodon loop, particularly at the first letter of the anticodon.…”

Triplet-encoded prebiotic RNA aminoacylation

“…The realization that tRNA identity determinants -used by aminoacyl-tRNA synthetases to determine whether a tRNA is cognate -do not always include the anticodon, resulted in a major conceptual advance (15,16). It was found that many identity determinants are clustered in the tRNA acceptor stem (17), indeed in one case identity is determined by a single base pair in the acceptor stem (18)(19)(20). This led to the suggestion that a 'second genetic code' is written in the acceptor stem of tRNA and read by aa-tRNA synthetases (21).…”

Anticodon sequence determines the impact of mistranslating tRNAAlavariants

“…Aminoacyl-tRNA synthetases recognize their cognate tRNAs through individual bases or structural motifs within the tRNA called identity elements [15][16][17]. For most tRNAs, the anticodon is the main identity element, providing a direct link between the genetic code and amino acid being incorporated.…”