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Paradigm-Changing Mechanism is Revealed for the Control of Gene Expression in Bacteria

A new study led by researchers at NYU Langone Medical Center is shedding new light on the action of Rho, a key regulatory protein in E. coli and many other bacteria. The study, published in the Jan. 14, 2010 issue of Nature, reveals a new paradigm to understand the molecular principles of gene transcription. This work could potentially lead to the development of new types of antibiotics that could target Rho and its crucial functions.

Rho – discovered in 1969 -- is the first transcription termination factor described in bacteria and other organisms. It acts as a red light to gene transcription and is essential for survival in many bacterial species. But the actual mechanism by which it works has been unknown. It was postulated that Rho loads onto RNA at a specific site and then translocates along the nascent transcript in pursuit of the moving RNA polymerase that is in the process of RNA synthesis. Once the RNA polymerase is paused, Rho has the chance to catch up and terminate transcription. In the new study researchers at the NYU Langone Medical Center challenge this textbook paradigm and provide a completely new mechanism of the Rho termination process.

The authors provide compelling experimental evidence against previously proposed “passive” models of Rho termination. Instead, they present direct evidence for an allosteric mechanism in which specific conformational changes in RNA polymerase catalytic center are responsible for Rho termination. This model provides a general conceptual framework from which to understand the molecular principles of all termination mechanisms. In addition, the study shows that Rho binds tightly to RNA polymerase throughout the transcription cycle, both in vitro and in vivo. This striking observation implies that Rho acts like a “subunit” of RNA polymerase that switches to the termination mode as soon as a sufficiently long segment of unprotected transcript emerges from RNA polymerase onto which Rho can load.
 
 

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