tRNA as an assembly chaperone for a macromolecular transcription-processing complex
Transfer RNAs (tRNAs) are widely recognized for their role in translation. Here, we describe a previously unidentified function of tRNA as an assembly chaperone. During poxviral infection, tRNA<sup>Gln/Arg</sup> lacking the anticodon mcm<sup>5</sup>s<sup>2</sup>U34 modification is specifically sequestered from the cellular tRNA pool to promote formation of a multisubunit poxviral RNA polymerase complex (vRNAP). Cryo-electron microscopy analysis of assembly intermediates illustrates how tRNA<sup>Gln/Arg</sup> orchestrates the recruitment of transcription and mRNA processing factors to vRNAP where it controls the transition to the preinitiation complex. This is achieved by an induced fit mechanism that internalizes anticodon base G36 into the anticodon stem, creating a noncanonical tRNA structure and selecting a defined tRNA modification pattern. The role of tRNA as an assembly chaperone extends to the pathogenic Mpox virus, which features a similar vRNAP.
Authors
- Tao Pan (ORCID: https://orcid.org/0000-0003-1096-8405)
- Takumi Okuda (ORCID: https://orcid.org/0000-0002-2136-6525)
- Utz Fischer (ORCID: https://orcid.org/0000-0002-1465-6591)
- Alexander Hüttenhofer
- Bettina Warscheid (ORCID: https://orcid.org/0000-0001-5096-1975)
- Claudia Höbartner (ORCID: https://orcid.org/0000-0002-4548-2299)
- Manisha Dixit (ORCID: https://orcid.org/0000-0001-6350-4677)
- J. Bartuli
- Asisa Volz (ORCID: https://orcid.org/0000-0001-8757-3896)
- Matthias David Erlacher
- Johannes P. Zimmermann (ORCID: https://orcid.org/0000-0001-5692-2096)
- Clemens Grimm (ORCID: https://orcid.org/0000-0001-9085-5130)
- Stefan Jungwirth
Institutions
- National Institutes of Health (US)
- Innsbruck Medical University (AT)
- University of Veterinary Medicine Hannover, Foundation (DE)
- University of Würzburg (DE)
- University of Chicago (US)
- National Heart, Lung, and Blood Institute (US)
- Helmholtz Centre for Infection Research (DE)
- Helmholtz Institute for RNA-based Infection Research (DE)
Publication Details
- Journal
- Nature Structural & Molecular Biology
- Published
- 2025-09-04
- DOI
- https://doi.org/10.1038/s41594-025-01653-y
- Citations
- 2
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- Deutsche Forschungsgemeinschaft
- Volkswagen Foundation
- Austrian Science Fund
- Julius-Maximilians-Universität Würzburg