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Co-translational determination of quaternary structures in chaperone factories

ABSTRACT: The HSP90/R2TP quaternary chaperone assembles key cellular machines, including the three nuclear RNA polymerases and many non-coding RNPs. Here, we characterized the RNA associated to R2TP and found that it binds many partners co-translationally. Its co-translational interactome further reveals many novel potential clients and identifies clients bound only co-translationally, only post-translationally, or both. For pairs of subunits assembling together and bound co-translationally by R2TP, only a marginal proportion of their mRNAs is co-localized and co-translated. Instead, the HSP90 and R2TP chaperones induce the formation of condensates accumulating client mRNAs and thus favoring co-translational interactions between chaperones and clients. The R2TP then 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. Assembly of protein complexes is thus initiated early by chaperones and this mechanism, dubbed co-translational chaperone channeling (cha-cha), substitutes for the rarity of co-localized/co-translated mRNAs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE291802 | GEO | 2026/01/13

REPOSITORIES: GEO

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Co-translational determination of quaternary structures in chaperone factories

Project description:The HSP90/R2TP quaternary chaperone assembles key cellular machines, including the three nuclear RNA polymerases and many non-coding RNPs. Here, we show that the R2TP binds many partners co-translationally. Remarkably, its co-translational interactome reveals many novel potential clients, and side-by-side comparison of RIP-seq and quantitative proteomics identifies clients bound only co-translationally, only post-translationally or both. For pairs of subunits assembling together and bound co-translationally by R2TP, only a marginal proportion of their mRNAs is co-localized and co-translated. Instead, the HSP90 and R2TP chaperones induce the formation of dedicated factories, which are cytoplasmic R2TP foci accumulating client mRNAs, thus favoring co-translational interactions. The R2TP alternates between co- and post-translational steps in a cycle regulated by ATP: following co-translational loading, it accompanies completed subunits towards their partners and becomes released following ATP hydrolysis. Assembly of protein complexes is thus initiated early by chaperones and this mechanism, dubbed co-translational chaperone channeling (cha-cha), substitutes for the rarity of co-localized/co-translated mRNAs.

2026-01-06 | PXD061298 | Pride

Post-translational Regulation of FNIP1: a Rheostat for the Molecular Chaperone Hsp90

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A specialized Hsp90 co-chaperone network regulates steroid hormone receptor response to ligand

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c-Abl Dependent Tyrosine Phosphorylation of theCo-chaperone Aha1 Regulates Interaction with Hsp90

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TSAA

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2014-10-24 | E-MTAB-2027 | biostudies-arrayexpress

c-Abl Dependent Tyrosine Phosphorylation of theCo-chaperone Aha1 Regulates Interaction with Hsp90

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Profiling of mRNA localization of nuclear-encoded mitochondrial proteins in zebrafish.

Project description:Current evidence suggests that nuclear-encoded mitochondrial proteins can be locally translated at the mitochondrial surface and co-translationally or post-translationally imported into mitochondria. mRNA localization on the mitochondrial membrane, a prerequisite for localized translation, remains uncharacterized in higher eukaryotic organisms. We employed fractionation-sequencing to profile mitochondria-associated mRNAs in zebrafish larvae. Our transcriptome-wide analysis reveals the localization of mRNAs of only 12% of the nuclear-encoded mitochondrial proteins to the mitochondrial surface, which suggests that post-translational import is the dominant mode of protein import to mitochondria. Additionally, the mRNAs which were localized to the mitochondrial membrane consisted mostly of those encoding proteins involved in mitochondrial dynamics, suggesting their site-specific translation. Finally, we show that the loss of function of the MIA pathway responsible for the post-translational import of a subclass of mitochondrial proteins, triggers mitochondrial localization of mRNAs encoding proteins that are imported to mitochondria via other pathways. Thus, our study suggests that mRNA targeting and localized translation could be relevant in higher eukaryotes to combat stress conditions affecting mitochondrial biogenesis in general.

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Head and Embryo 80S monosomes are much more translationally active than 80S in other tissues

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Bacteria differently regulate mRNA copy numbers to specifically respond to various stresses

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A systematic analysis of nuclear heat-shock protein 90 identifies a metazoan-specific regulatory module

Project description:Molecular chaperones such as heat-shock proteins (HSPs) help in protein folding and complex assembly processes. Their role in cytosol has been very well elucidated. Chaperones are also present in the nucleus, a compartment where proteins enter after being fully folded in the cytosol, raising an important question about chaperones function in this compartment. We have performed a systematic analysis of nuclear heat- shock protein 90 to identify regulatory functions of this chaperone in the nucleus. Combining physical and genetic interactomes with a cancer co-expression screen allowed us to define 'core functional interactors' of nuclear HSP90 consisting of five proteins. Using transcriptional studies we identified Host Cell Factor C1 (HCFC1) as a metazoan-specific transcriptional regulator that depends on HSP90 for its stability in the nucleus. We found that HSP90 is required for optimal activity of HCFC1 in transcription. Thus our study provides the first global insight into the function of nuclear HSP90.

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