Two for the price of one: RNA modification enzymes as chaperones

Abstract

Although folding of nascent proteins often requires assistance from molecular chaperones, the extent to which newly made RNAs need other macromolecules to help them reach their native states is less studied. One class of proteins and ribonucleoproteins (RNPs) that is proposed to assist RNA folding consists of the enzymes that modify RNA nucleosides. Of the more than 100 distinct modifications, the most abundant is pseudouridine, an isomer of uridine present in most types of RNA, including tRNA, rRNA, mRNA, and spliceosomal RNAs (1). Pseudouridine increases the rigidity of the RNA backbone and can enhance base stacking, stabilize base pairs, and alter RNA structure (2). Pseudouridine synthases fall into two categories, stand-alone enzymes and those pseudouridine synthases that function as part of archaeal and eukaryotic RNPs called box H/ACA RNPs. Although many stand-alone pseudouridine synthases are dispensable for viability of Escherichia coli and the budding yeast Saccharomyces cerevisiae , deletion of some tRNA pseudouridine synthases results in growth defects that can be complemented by catalytically inactive mutants (3⇓–5). Thus, these proteins are proposed to have a second function as tRNA chaperones (4, 5). Similarly, although the RNA moiety of box H/ACA RNPs guides the pseudouridine synthase to specific uridines (2), base-pairing between these box H/ACA RNAs and their pre-rRNA targets could also influence RNA folding (6). However, evidence that these proteins and RNPs act as chaperones is lacking, as is knowledge of the mechanisms by which they could function. In PNAS, Keffer-Wilkes et al. (7) use biophysical and genetic approaches to demonstrate that the stand-alone E. coli tRNA pseudouridine synthase B (TruB) assists tRNA folding in vitro, identify a molecular mechanism, and provide evidence that TruB is a tRNA chaperone in vivo. For relatively short molecules, tRNA biosynthesis is amazingly complex. All tRNAs are transcribed as precursors … [↵][1]1Email: sandra.wolin{at}yale.edu. [1]: #xref-corresp-1-1