title: 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.
authors.affiliation: Intramural Research Program, Eunice Kennedy Shriver NationalInstitute of Child Health and Human Development, NationalInstitutes of Health, Bethesda, MD, USA. maraiar@mail.nih.gov
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Maraia
authors.forename: Tek N
authors.initials: TN
authors.lastname: Lamichhane
mesh_terms: D000818:Animals; D004722:Endoribonucleases / Q000378:metabolism; D005092:Exonucleases / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D026721:RNA 3' End Processing / Q000502:physiology*; D012320:RNA Polymerase III / Q000378:metabolism; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D043262:Ribonuclease P / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism
chemical_list: D018832:Molecular Chaperones; D012322:RNA Precursors; D012331:RNA, Fungal; D016601:RNA-Binding Proteins; D012320:RNA Polymerase III; D004722:Endoribonucleases; D005092:Exonucleases; C110250:RNase Z; D043262:Ribonuclease P