TRNA as an assembly chaperone for a macromolecular transcription-processing complex

ABSTRACT: 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 tRNAGln/Arg lacking the anticodon mcm5s2U modification is specifically recruited from the cellular tRNA pool to a multi-subunit poxviral RNA polymerase complex (vRNAP), where it controls the transition to the pre-initiation complex upon infection. Cryo-EM analysis of assembly intermediates illustrates how tRNAGln/Arg orchestrates the recruitment of transcription and mRNA processing factors to vRNAP. The atomic vRNAP structures reveal an induced-fit mechanism that internalizes anticodon base G36 into the anticodon stem creating a non-canonical tRNA structure and selecting a defined tRNA modification pattern. The role of tRNA as assembly chaperone extends to the pathogenic MPXV due to the high conservation of vRNAP.

INSTRUMENT(S):

ORGANISM(S): Vaccinia Virus Glv-1h68 Homo Sapiens (human)

TISSUE(S): Hela-s3 Cell, Malignant Cell

SUBMITTER: Julian Bender  

LAB HEAD: Bettina Warscheid

PROVIDER: PXD057359 | Pride | 2025-11-24

REPOSITORIES: Pride