3′ processing of eukaryotic precursor tRNAs

Abstract Biogenesis of eukaryotic tRNAs requires transcription by RNA polymerase III and subsequent processing. 5′ processing of precursor tRNA occurs by a single mechanism, cleavage by RNase P, and usually occurs before 3′ processing although some conditions allow observation of the 3′‐first pathway. 3′ processing is relatively complex and is the focus of this review. Precursor RNA 3′ end formation begins with pol III termination generating a variable length 3′ oligo(U) tract that represents an underappreciated and previously unreviewed determinant of processing. Evidence that the pol III‐intrinsic 3′ exonuclease activity mediated by Rpc11p affects 3′ oligo(U) length is reviewed. In addition to multiple 3′ nucleases, precursor tRNA (pre‐tRNA) processing involves La and Lsm, distinct oligo(U)‐binding proteins with proposed chaperone activities. 3′ processing is performed by the endonuclease RNase Z or the exonuclease Rex1p (possibly others) along alternate pathways conditional on La. We review a Schizosaccharomyces pombe tRNA reporter system that has been used to distinguish two chaperone activities of La protein to its two conserved RNA binding motifs. Pre‐tRNAs with structural impairments are degraded by a nuclear surveillance system that mediates polyadenylation by the TRAMP complex followed by 3′ digestion by the nuclear exosome which appears to compete with 3′ processing. We also try to reconcile limited data on pre‐tRNA processing and Lsm proteins which largely affect precursors but not mature tRNAs. A pathway is proposed in which 3′ oligo(U) length is a primary determinant of La binding with subsequent steps distinguished by 3′ endo versus exo nucleases, chaperone activities, and nuclear surveillance. WIREs RNA 2011 2 362–375 DOI: 10.1002/wrna.64 This article is categorized under: RNA Structure and Dynamics > RNA Structure, Dynamics, and Chemistry RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications RNA Processing > tRNA Processing