Modifying Mitochondrial tRNAs: Delivering What the Cell Needs

Abstract

Protein synthesis is critically dependent on transfer (t)-RNAs, but the factors regulating tRNA function are poorly understood. In this issue of Cell Metabolism, Wei et al. (2015) show that Cdk5 regulatory subunit-associated protein-like-1 synchronizes mitochondrial and cytosolic translation in response to external stress, providing key insight into the pathogenesis of a common inherited mitochondrial disease.

Lack of tRNA-i6A modification causes mitochondrial-like metabolic deficiency in S. pombe by limiting activity of cytosolic tRNATyr, not mito-tRNA

“…The ectopic tRNA devoid of i6A37 when overexpressed by approximately threefold nicely fits with and significantly extends previous results that indicate that i6A37 increases the activity of tRNA by about threefold (Lamichhane et al 2013a). It is important to note here that S. cerevisiae, S. pombe and humans modify different subsets of tRNAs with i6A37, both the cy-and mt-tRNAs (Lamichhane et al 2011(Lamichhane et al , 2013bHorvath and Chinnery 2015;Wei et al 2015). Differences in tRNA-i6A37 subsets is part of a wider variability in the overall tRNA gene content of different eukaryotic genomes and in the tRNA anticodon modification systems, which together with corresponding codon-content may contribute to plasticity of genetic information (Iben and Maraia 2012;Maraia and Iben 2014).…”

Canis familiaris tissues are characterized by different profiles of cytokinins typical of the tRNA degradation pathway

“…Inside the mammalian cell, TRIT1 facilitates the isopentenylation of A37 in a subset of cytosolic and mitochondrial tRNAs (10,26). TRIT1 modification alters structure stability, ribosome interactions, and translation efficacy (13,27,28). TRIT1 has also been implicated in tRNA gene-mediated transcriptional silencing (26), in amyloid fiber folding (29), as a tumor suppressor (30), and in selenoprotein regulation (31).…”

“…Estimations of cdk5rap1 expression (available from www.proteinatlas.org) were ubiquitous for all tissues, although no protein expression data were available (33). In tRNA, CDK5RAP1 modifications function in the same manner as the TRIT1 modifications, whereby they alter stability, interactions with the ribosome, and translation (27,28). CDK5RAP1 also acts as an inhibitor of CDK5 to maintain healthy neuronal development and neurogenesis (37).…”

The Origins and Roles of Methylthiolated Cytokinins: Evidence From Among Life Kingdoms

“…In mammals, cyclin dependent kinase 5 regulatory subunit-associated protein 1 (CDK5RAP1) is a type of radical SAM enzyme that reductively cleaves S-adenosyl-L-methionine ( Atta et al, 2010 ), with homology to miaB ( Kaminska et al, 2008 ; Reiter et al, 2012 ). CDK5RAP1 is responsible for methylthiolation of tRNA-bound CKs and has roles in altering stability of tRNA molecules, interactions with ribosomes and translation ( Jenner et al, 2010 ; Horvath and Chinnery, 2015 ). The presence of unbound 2MeS-CK metabolites was recently reported from the surveyed canine tissues and human cell cultures ( Seegobin et al, 2018 ; Aoki et al, 2019b ).…”