title: Analysis of orthologous groups reveals archease and DDX1 as tRNA splicing factors.
abstract: RNA ligases have essential roles in many cellular processes in eukaryotes, archaea and bacteria, including in RNA repair and stress-induced splicing of messenger RNA. In archaea and eukaryotes, RNA ligases also have a role in transfer RNA splicing to generate functional tRNAs required for protein synthesis. We recently identified the human tRNA splicing ligase, a multimeric protein complex with RTCB (also known as HSPC117, C22orf28, FAAP and D10Wsu52e) as the essential subunit. The functions of the additional complex components ASW (also known as C2orf49), CGI-99 (also known as C14orf166), FAM98B and the DEAD-box helicase DDX1 in the context of RNA ligation have remained unclear. Taking advantage of clusters of eukaryotic orthologous groups, here we find that archease (ARCH; also known as ZBTB8OS), a protein of unknown function, is required for full activity of the human tRNA ligase complex and, in cooperation with DDX1, facilitates the formation of an RTCB-guanylate intermediate central to mammalian RNA ligation. Our findings define a role for DDX1 in the context of the human tRNA ligase complex and suggest that the widespread co-occurrence of archease and RtcB proteins implies evolutionary conservation of their functional interplay.
authors.affiliation: 1] Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), A-1030 Vienna, Austria [2] European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Popow
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), A-1030 Vienna, Austria.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jurkin
authors.affiliation: IMP/IMBA Bioinformatics Core Facility, Research Institute of Molecular Pathology (IMP), A-1030 Vienna, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schleiffer
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), A-1030 Vienna, Austria.
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D020134:Catalytic Domain; D002470:Cell Survival; D017124:Conserved Sequence; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D019143:Evolution, Molecular; D006801:Humans; D009097:Multienzyme Complexes / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D011506:Proteins; D011130:RNA Ligase (ATP) / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D012326:RNA Splicing; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins
chemical_list: D002352:Carrier Proteins; C000595051:FAM98B protein, human; D009097:Multienzyme Complexes; D011506:Proteins; D016601:RNA-Binding Proteins; C556193:RTCB protein, human; C000590560:ZBTB8OS protein, human; D012343:RNA, Transfer; C086252:DDX1 protein, human; D053487:DEAD-box RNA Helicases; C108348:tRNA splicing ligase; D011130:RNA Ligase (ATP)