Crosstalk between the tRNA methyltransferase Trm1 and RNA chaperone La influences eukaryotic tRNA maturation

Abstract

tRNAs undergo an extensive maturation process involving post-transcriptional modifications often associated with tRNA structural stability and promoting the native fold. Impaired post-transcriptional modification has been linked to human disease, likely through defects in translation, mitochondrial function, and increased susceptibility to degradation by various tRNA decay pathways. More recently, evidence has emerged that bacterial tRNA modification enzymes can act as tRNA chaperones to guide tRNA folding in a manner independent from catalytic activity. Here, we provide evidence that the fission yeast tRNA methyltransferase Trm1, which dimethylates nuclear- and mitochondrial-encoded tRNAs at G26, can also promote tRNA functionality in the absence of catalysis. We show that wild type and catalytic-dead Trm1 are active in an in vivo tRNA-mediated suppression assay and possess in vitro RNA folding activity, suggesting an alternate function as a tRNA chaperone. Further, we demonstrate crosstalk between Trm1 and the RNA chaperone La, with La binding to the 3′ end and body of nascent pre-tRNA inhibiting tRNA dimethylation in vivo and in vitro. Collectively, these results support the hypothesis for multi-functional tRNA modification enzymes that combine catalytic and non-catalytic activities to shape tRNA structure and function.