Letter | Published:

Analysis of orthologous groups reveals archease and DDX1 as tRNA splicing factors

Nature volume 511, pages 104107 (03 July 2014) | Download Citation

Abstract

RNA ligases have essential roles in many cellular processes in eukaryotes, archaea and bacteria, including in RNA repair1,2 and stress-induced splicing of messenger RNA3. In archaea and eukaryotes, RNA ligases also have a role in transfer RNA splicing to generate functional tRNAs required for protein synthesis4,5,6,7. 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 subunit8. 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.

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Acknowledgements

We would like to thank S. Ameres, B. Beckmann, R. Hartmann, M. Hentze, M. Jantsch, B. Klaus, B. Mair, A. F. Nielsen, J.-M. Peters, T. Rapoport, R. Schroeder and S. Weitzer for help and advice, S. Bandini for the preparation of Flag–TSEN2 cell lines and critical discussions and J. Dammann and T. Lendl for technical assistance. This work has been funded by the Fonds zur Förderung der wissenschaftlichen Forschung (P24687), the GEN-AU 3 research programme (820982 Non-coding RNAs) (J.P.) and the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (J.M.).

Author information

Affiliations

  1. Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), A-1030 Vienna, Austria

    • Johannes Popow
    • , Jennifer Jurkin
    •  & Javier Martinez
  2. European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany

    • Johannes Popow
  3. IMP/IMBA Bioinformatics Core Facility, Research Institute of Molecular Pathology (IMP), A-1030 Vienna, Austria

    • Alexander Schleiffer

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Contributions

J.P. designed and carried out experiments and wrote the manuscript, J.J. designed and carried out experiments and contributed to writing the manuscript, A.S. performed bioinformatic analysis of archease and contributed to writing the manuscript, J.M. designed the experiments and contributed to writing the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Javier Martinez.

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DOI

https://doi.org/10.1038/nature13284

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