Queuosine modification of tRNA: its divergent role in cellular machinery

Abstract

tRNAs possess a high content of modified nucleosides, which display an incredible structural variety. These modified nucleosides are conserved in their sequence and have important roles in tRNA functions. Most often, hypermodified nucleosides are found in the wobble position of tRNAs, which play a direct role in maintaining translational efficiency and fidelity, codon recognition, etc. One of such hypermodified base is queuine, which is a base analogue of guanine, found in the first anticodon position of specific tRNAs (tyrosine, histidine, aspartate and asparagine tRNAs). These tRNAs of the ‘Q-family’ originally contain guanine in the first position of anticodon, which is post-transcriptionally modified with queuine by an irreversible insertion during maturation. Queuine is ubiquitously present throughout the living system from prokaryotes to eukaryotes, including plants. Prokaryotes can synthesize queuine de novo by a complex biosynthetic pathway, whereas eukaryotes are unable to synthesize either the precursor or queuine. They utilize salvage system and acquire queuine as a nutrient factor from their diet or from intestinal microflora. The tRNAs of the Q-family are completely modified in terminally differentiated somatic cells. However, hypomodification of Q-tRNA (queuosine-modified tRNA) is closely associated with cell proliferation and malignancy. The precise mechanisms of queuine- and Q-tRNA-mediated action are still a mystery. Direct or indirect evidence suggests that queuine or Q-tRNA participates in many cellular functions, such as inhibition of cell proliferation, control of aerobic and anaerobic metabolism, bacterial virulence, etc. The role of Q-tRNA modification in cellular machinery and the signalling pathways involved therein is the focus of this review.