Analysis of orthologous groups reveals archease and DDX1 as tRNA splicing factors
- Nature. 2014 Jul 3;511(7507):104-7. doi: 10.1038/nature13284.
- 1. 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.
- 2. Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), A-1030 Vienna, Austria.
- 3. IMP/IMBA Bioinformatics Core Facility, Research Institute of Molecular Pathology (IMP), A-1030 Vienna, Austria.
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.