TRiC/CCT chaperonin governs RNA polymerase II activity in the nucleus to support RNA homeostasis.

Eukaryotic tailless complex polypeptide 1 ring complex/Chaperonin containing tailless complex polypeptide 1 (TRiC/CCT) chaperonin is typically considered a cytosolic machine mediating polypeptide folding and assembly of protein complexes. Here, we investigated the nuclear role of TRiC/CCT. Use of a TRiC/CCT temperature-sensitive allele revealed increased production of nascent RNA leading to the accumulation of noncoding transcripts. TRiC/CCT was associated with RNA polymerase II (RNAPII) in vitro and in vivo, including when bound to DNA. Heat treatment of the TRiC/CCT ts chaperonin stabilized the RNAPII complex association and binding to the actin and tubulin substrates. Expression of the Huntingtin protein Htt correlated with lowered RNA production and a decreased association between the RNAPII and TRiC/CCT complexes. Together, our presented data support a model where TRiC/CCT regulates the global activity of RNAPII in reaction to the status of proteostasis. Overall, our work reveals an avenue by which TRiC/CCT contributes to homeostasis by regulating the activity of nuclear RNAPII.