On the Track of the Missing tRNA Genes: A Source of Non-Canonical Functions?

Ricardo Ehrlich,Ignacio López,Cora Chalar,Mónica Marín,Marcos Davyt

doi:10.3389/fmolb.2021.643701

Ricardo Ehrlich, Ignacio López + Show 3 more

Open Access

https://doi.org/10.3389/fmolb.2021.643701

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Abstract

Cellular tRNAs appear today as a diverse population of informative macromolecules with conserved general elements ensuring essential common functions and different and distinctive features securing specific interactions and activities. Their differential expression and the variety of post-transcriptional modifications they are subject to, lead to the existence of complex repertoires of tRNA populations adjusted to defined cellular states. Despite the tRNA-coding genes redundancy in prokaryote and eukaryote genomes, it is surprising to note the absence of genes coding specific translational-active isoacceptors throughout the phylogeny. Through the analysis of different releases of tRNA databases, this review aims to provide a general summary about those “missing tRNA genes.” This absence refers to both tRNAs that are not encoded in the genome, as well as others that show critical sequence variations that would prevent their activity as canonical translation adaptor molecules. Notably, while a group of genes are universally missing, others are absent in particular kingdoms. Functional information available allows to hypothesize that the exclusion of isodecoding molecules would be linked to: 1) reduce ambiguities of signals that define the specificity of the interactions in which the tRNAs are involved; 2) ensure the adaptation of the translational apparatus to the cellular state; 3) divert particular tRNA variants from ribosomal protein synthesis to other cellular functions. This leads to consider the “missing tRNA genes” as a source of putative non-canonical tRNA functions and to broaden the concept of adapter molecules in ribosomal-dependent protein synthesis.

Highlights

Over the last few years, tRNA has become the subject of intense research where technological and conceptual advances converge from integrative biology to pathology and biotechnology
Missing tRNA Genes three-dimensional structure (Kim et al, 1974), still pose complex challenges centered on their structure and functions, despite the remarkable advances in sequencing techniques and structural studies of nucleic acids (Dittmar et al, 2006; Pang et al, 2014; Ferro and Ignatova, 2015; Zhang et al, 2015; Evans et al, 2017; Shigematsu et al, 2017; Kimura et al, 2020; Pinkard et al, 2020; Zhang et al, 2020)
As central adapter molecules in protein biosynthesis, the diversity of tRNA isoacceptors or isotypes, isodecoders, and modified states thereof, ensures the transmission of information from a nucleotide to an amino acid sequence. tRNAs participate in the adjustment of the translation machinery and its kinetics, as well as in cotranslational folding of peptides in order to meet the cellular requirements in terms of repertoire and relative amount of proteins (Gingold et al, 2014; Kirchner and Ignatova, 2015; Kirchner et al, 2017; Marín et al, 2017; Rak et al, 2018)

Summary

Introduction

Over the last few years, tRNA has become the subject of intense research where technological and conceptual advances converge from integrative biology to pathology and biotechnology. Cellular tRNAs appear today as a diverse population of informative macromolecules with conserved general elements ensuring essential common functions and different and distinctive features securing specific interactions and activities Their differential expression and the variety of posttranscriptional modifications they are subject to, lead to the existence of complex repertoires of tRNA populations adjusted to defined cellular states (Dittmar et al, 2006; Pavon-Eternod et al, 2009; Gingold et al, 2014; Pang et al, 2014; Goodarzi et al, 2016; Sagi et al, 2016; Kimura et al, 2020; Pinkard et al, 2020). Evidence has accumulated on the existence of particular species of isoacceptor tRNAs for specific amino acids, defined according to their structural characteristics and anticodon, with different functionalities (Giannouli et al, 2009; Rudinger-Thirion et al, 2011; Rogers et al, 2012; Torres, 2019)

Objectives

Conclusion