Revisiting tRNA chaperones: new players in an ancient game

Abstract

tRNAs undergo an extensive maturation process including posttranscriptional modifications that influence secondary and tertiary interactions. Precursor and mature tRNAs lacking key modifications are often recognized as aberrant and subsequently targeted for decay, illustrating the importance of modifications in promoting structural integrity. tRNAs also rely on tRNA chaperones to promote the folding of misfolded substrates into functional conformations. The best characterized tRNA chaperone is the La protein, which interacts with nascent RNA polymerase III transcripts to promote folding and offers protection from exonucleases. More recently, certain tRNA modification enzymes have also been demonstrated to possess tRNA folding activity distinct from their catalytic activity, suggesting that they may act as tRNA chaperones. In this review, we will discuss pioneering studies relating posttranscriptional modification to tRNA stability and decay pathways, present recent advances into the mechanism by which the RNA chaperone La assists pre-tRNA maturation, and summarize emerging research directions aimed at characterizing modification enzymes as tRNA chaperones. Together, these findings shed light on the importance of tRNA folding and how tRNA chaperones, in particular, increase the fraction of nascent pre-tRNAs that adopt a folded, functional conformation.

Molecular mechanism of tRNA binding by the Escherichia coli N7 guanosine methyltransferase TrmB

“…Building on the mechanism of TrmB described here, it will be interesting to analyze in the future whether and how TrmB influences tRNA folding as it likely disrupts critical tertiary interactions in the tRNA elbow region. Thus, TrmB has the potential to also act as a tRNA chaperone as previously reported for E. coli TruB and TrmA ( 32 , 50 , 51 ).…”

The life and times of a tRNA

“…The La protein also has a major non-catalytic role in affecting the pathways of 3' end formation of pre-tRNAs. La protein is an abundant nuclear protein, which binds pre-tRNAs (Rinke and Steitz 1982) at their 3' oligo(U) ends (Stefano 1984;Teplova et al 2006), for review see (Wolin and Cedervall 2002;Maraia and Bayfield 2006;Porat et al 2021). La binding leads to endonucleolytic cleavage of the 3' trailer sequence of the pre-tRNA, and protects the 3' end of the pre-tRNA from exonucleases in S. cerevisiae (Yoo and Wolin 1997).…”

The fission yeast methyl phosphate capping enzyme Bmc1 guides 2’-O-methylation of the U6 snRNA

“…Taken together, this work adds to the growing body of literature on the catalytic-independent functions of RNA modification enzymes (reviewed in (63)). While this raises questions as to the precise function of Bmc1 catalytic activity on the 5’ end of U6, in vitro binding assays showed that catalytic activity of the human MePCE promotes 7SK retention following catalysis (64).…”