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bioRxiv · 10.1101/2023.04.10.536203

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

Leone, S.·Srivastava, A.·Hummel, B.·Tittel, L.·Aprile-Garcia, F.·Herrero-Ruiz, A.·Rawat, P.·Willis, A. E.·Sawarkar, R.
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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 (Pol III) such as tRNA and 5S rRNA. Global chromatin profiling revealed that HSP70 binds genomic sites of transcription by Pol III. Detailed biochemical analyses showed that HSP70 facilitates transcription of its target non-coding RNA by binding to Pol III. 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 neurodegeneration and cancer.

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Leone, S., Srivastava, A., Hummel, B., Tittel, L., Aprile-Garcia, F., Herrero-Ruiz, A., Rawat, P., Willis, A. E., Sawarkar, R.. 2023-04-10. HSP70 binds to specific non-coding RNA and regulates human RNA Polymerase III. https://doi.org/10.1101/2023.04.10.536203

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