Résumé
The HSP90/R2TP quaternary chaperone assembles key cellular machines, including the three nuclear RNA polymerases and many non-coding RNPs. Here, we characterize the RNAs associated with R2TP and find that it binds many proteins co-translationally. Its co-translational interactome reveals potential clients and distinguishes clients bound only co-translationally, only post-translationally, or both. For subunits assembling together in the same complex and bound co-translationally by R2TP, only a marginal proportion of their mRNAs is co-localized and co-translated. Instead, HSP90 and R2TP induce the formation of polysome condensates accumulating these chaperones and specific client mRNAs, thus favoring co-translational interactions between them. During the assembly process, R2TP cycles between co- and post-translational steps and this is regulated by ATP: it binds co-translationally in absence of ATP and becomes released from post-translational assembly intermediates by ATP hydrolysis. This co-translational mechanism, named co-translational chaperone channeling (cha-cha), substitutes for the rarity of co-localized/co-translated mRNAs. In turn, chaperones have the remarkable ability to spatially organize the translational apparatus in the cytoplasm.