We are thrilled to announce Susanta’s latest achievement in publishing his latest groundbreaking findings in a preprint on bioRxiv!
Susanta's work has unravelled a crucial role for the Ribosome Quality Control (RQC) mechanism in mitigating the cytotoxic effects of 5-Fluorouracil (5FU), a cornerstone in cancer chemotherapeutic regimens. The study delves into the intricate world of RNA-dependent 5FU cytotoxicity, shedding light on the previously unclear cellular responses to its impact on RNA metabolism.
In a nutshell, the research reveals that RQC acts as a guardian against translation stress caused by ribosome collisions during 5FU treatment. Susanta's findings demonstrate that acute 5FU exposure triggers a cascade of events, including the rapid induction of the mTOR signaling pathway, heightened mRNA translation initiation, and increased ribosome collisions, all of which activate the RQC mechanism. Importantly, this work highlights that a deficiency in RQC, specifically due to the depletion of ZNF598, intensifies 5FU-induced cell death. Excitingly, this detrimental effect can be reversed by inhibiting mTOR or repressing mRNA translation initiation. We also unveiled a previously unknown mTOR-dependent mechanism that enhances the RQC process, mitigating the cytotoxicity of 5FU and challenging its anticancer efficacy.
We extend our heartfelt congratulations to Susanta for this remarkable achievement and express our gratitude to all collaborators who contributed to this groundbreaking work!