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. 2024 Feb 15;84(4):687-701.e7.
doi: 10.1016/j.molcel.2024.01.001. Epub 2024 Jan 23.

HSP70 binds to specific non-coding RNA and regulates human RNA polymerase III

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Free article

HSP70 binds to specific non-coding RNA and regulates human RNA polymerase III

Sergio Leone et al. Mol Cell. .
Free article

Abstract

Molecular chaperones are critical for protein homeostasis and are implicated in several human pathologies such as neurodegeneration and cancer. While the binding of chaperones to nascent and misfolded proteins has been studied in great detail, the direct interaction between chaperones and RNA has not been systematically investigated. Here, we provide the evidence for widespread interaction between chaperones and RNA in human cells. We show that the major chaperone heat shock protein 70 (HSP70) binds to non-coding RNA transcribed by RNA polymerase III (RNA Pol III) such as tRNA and 5S rRNA. Global chromatin profiling revealed that HSP70 binds genomic sites of transcription by RNA Pol III. Detailed biochemical analyses showed that HSP70 alleviates the inhibitory effect of cognate tRNA transcript on tRNA gene transcription. Thus, our study uncovers an unexpected role of HSP70-RNA interaction in the biogenesis of a specific class of non-coding RNA with wider implications in cancer therapeutics.

Keywords: HSP70; RNA polymerase III; RNA-binding proteome; RNA-protein interaction; heat-shock proteins; molecular chaperones; non-coding RNA; proteostasis; tRNA; transcription.

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Conflict of interest statement

Declaration of interests S.L. and P.A. are employees of AstraZeneca. F.A.-G. is employee of Cytena GmbH.