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bioRxiv · 10.1101/2024.09.26.615188

TRiC/CCT Chaperonin Governs RNA Polymerase II Activity in the Nucleus to Support RNA Homeostasis

Gvozdenov, Z.·Peng, A. Y. T.·Biswas, A.·Barcutean, Z.·Gestaut, D.·Frydman, J.·Struhl, K.·Freeman, B. C.
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Abstract

The chaperonin TRiC/CCT is a large hetero-oligomeric ringed-structure that is essential in eukaryotes. While present in the nucleus, TRiC/CCT is typically considered to function in the cytosol where it mediates nascent polypeptide folding and the assembly/disassembly of protein complexes. Here, we investigated the nuclear role of TRiC/CCT. Inactivation of TRiC/CCT resulted in a significant increase in the production of nascent RNA leading to the accumulation of noncoding transcripts. The influence on transcription was not due to cytoplasmic TRiC/CCT-activities or other nuclear proteins as the effect was observed when TRiC/CCT was evicted from the nucleus and restricted to the cytoplasm. Rather, our data support a direct role of TRiC/CCT in regulating RNA polymerase II activity, as the chaperonin modulated nascent RNA production both in vivo and in vitro. Overall, our studies reveal a new avenue by which TRiC/CCT contributes to cell homeostasis by regulating the activity of nuclear RNA polymerase II.

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Gvozdenov, Z., Peng, A. Y. T., Biswas, A., Barcutean, Z., Gestaut, D., Frydman, J., Struhl, K., Freeman, B. C.. 2024-09-26. TRiC/CCT Chaperonin Governs RNA Polymerase II Activity in the Nucleus to Support RNA Homeostasis. https://doi.org/10.1101/2024.09.26.615188

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