Scientists uncover a hidden mechanism that drives RNA synthesis
Scientists have long been fascinated by two promising classes of antibiotics that disable RNA polymerase (RNAP). They knew that these drugs could grind gene expression to a halt in several pathogens, including the bacterium behind tuberculosis, by binding to specific locations in RNAP. But despite decades of study, a key question remained: What process are the drugs actually targeting?
Scientists have discovered a hidden mechanism that drives RNA synthesis, a crucial process in all living organisms. A new study published in the Proceedings of the National Academy of Sciences reveals that the enzyme ribonucleic acid polymerase (RNAP) requires a specific moving part to briefly swing into place to stabilize RNA synthesis.
This discovery was made possible by researchers using antibiotics as tools to clarify the finer points of RNAP function. The findings not only provide a better understanding of how certain antibiotics disable RNA polymerase in pathogens, including the bacterium responsible for tuberculosis, but also lay the groundwork for developing next-generation antibiotics.
The mechanism involves a previously unrecognized movement of the rim helices/F-loop, which stabilizes the enzyme as it adds each new RNA building block. When antibiotics prevent this movement, they effectively halt RNAP and take their respective pathogens offline. This discovery could lead to the development of more effective treatments for tuberculosis, where resistance to existing treatments continues to rise.
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