Post-transcriptional negative feedback regulation of proteostasis through the Dis3 ribonuclease and its disruption by polyQ-expanded Huntingtin.

ABSTRACT: When proteostasis is disrupted by stresses such as heat shock, the heat stress response will be stimulated, leading to up-regulation of molecular chaperones by transcriptional activation and mRNA stabilization for restoring proteostasis. Although the mechanisms for their transcriptional activation have been clearly defined, how chaperone mRNAs are stabilized remains largely unknown. Starting by exploring the coupling between the apparently unrelated RNA degradation and protein quality control (PQC) systems, we show that the Dis3 ribonuclease, catalytic subunit of the RNA exosome required for RNA degradation, suppresses PQC activity in unstressed cells by degrading mRNAs encoding the Hsp70 cofactors Sis1, Ydj1 and Fes1, as well as some other chaperones or PQC factors, thereby limiting their

SUBMITTER: Kong KE 

PROVIDER: S-EPMC6821268 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature