title: RtcB, a novel RNA ligase, can catalyze tRNA splicing and HAC1 mRNA splicing in vivo.
abstract: RtcB enzymes are novel RNA ligases that join 2',3'-cyclic phosphate and 5'-OH ends. The phylogenetic distribution of RtcB points to its candidacy as a tRNA splicing/repair enzyme. Here we show that Escherichia coli RtcB is competent and sufficient for tRNA splicing in vivo by virtue of its ability to complement growth of yeast cells that lack the endogenous "healing/sealing-type" tRNA ligase Trl1. RtcB also protects yeast trl1Δ cells against a fungal ribotoxin that incises the anticodon loop of cellular tRNAs. Moreover, RtcB can replace Trl1 as the catalyst of HAC1 mRNA splicing during the unfolded protein response. Thus, RtcB is a bona fide RNA repair enzyme with broad physiological actions. Biochemical analysis of RtcB highlights the uniqueness of its active site and catalytic mechanism. Our findings draw attention to tRNA ligase as a promising drug target.
authors.affiliation: Molecular Biology Program, Sloan-Kettering Institute, New York, New York 10065.
authors.forename: Naoko
authors.initials: N
authors.lastname: Tanaka
authors.affiliation: Molecular Biology Program, Sloan-Kettering Institute, New York, New York 10065.
authors.forename: Birthe
authors.initials: B
authors.lastname: Meineke
authors.affiliation: Molecular Biology Program, Sloan-Kettering Institute, New York, New York 10065. Electronic address: s-shuman@ski.mskcc.org.
authors.forename: Stewart
authors.initials: S
authors.lastname: Shuman
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry* / Q000502:physiology; D000926:Anticodon; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry*; D002384:Catalysis; D020134:Catalytic Domain; D004260:DNA Repair; D004926:Escherichia coli / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000502:physiology; D007438:Introns; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011130:RNA Ligase (ATP) / Q000737:chemistry*; D012326:RNA Splicing; D012343:RNA, Transfer / Q000737:chemistry*; D012097:Repressor Proteins / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*
chemical_list: D000926:Anticodon; D050976:Basic-Leucine Zipper Transcription Factors; D029968:Escherichia coli Proteins; C091341:HAC1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D012343:RNA, Transfer; D000604:Amino Acyl-tRNA Synthetases; C561935:RtcB protein, E coli; D011130:RNA Ligase (ATP)