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Rewriting 50-year old biological rule, scientists discover path to develop better antibiotics

Biology, for about half-a-century, has held that bacteria turn their genes with the help of a ‘sigma cycle’, which are factors that bind RNA polymerase to initiate transcription and then dissociate to allow elongation

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A new study has helped rewrite a 50-year-old biological rule on bacterial genes, which are functional units of DNA, and unveils new paths for understanding bacterial gene regulation and its evolution.

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The discovery has broad implications for microbiology, potentially influencing how researchers approach bacterial physiology, stress response and the development of antibiotics targeting transcription.

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This could also help develop better antibiotics or regulatory inhibitors that block infection mechanisms and design microorganisms that produce biofuels, biodegradable plastics, or therapeutic compounds efficiently, according to information shared by the Ministry of Science and Technology on Monday.

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For about half-a-century, biology has held that bacteria turn their genes with the help of a ‘sigma cycle’, which are factors that bind RNA polymerase to initiate transcription and then dissociate to allow elongation. Polymerase is an essential enzyme that synthesizes long chains of nucleic acids.

In their research published in the Proceedings of the National Academy of Sciences, researchers from the Bose Institute, India and Rutgers University, USA have now revealed that the cycle is not a universal phenomenon.

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They have found that, contrary to decades of scientific belief, the principal transcription initiation factor in bacteria remains bound to RNA polymerase throughout transcription, rather than being released after initiation. Transcription is the first step of gene expression where a specific segment of DNA is copied into a new, single-stranded RNA molecule by polymerase.

“Our work shows that in Bacillus subtilis, the sigma factor stays attached to RNA polymerase all the way through the transcription process,” said Dr Jayanta Mukhopadhyay from the Bose Institute. “This fundamentally changes how we think about bacterial transcription and gene regulation.”

Using a combination of different modern techniques, the researchers watched the sigma factor’s behaviour in real time and analysed the transcription complexes and elongation processes.

“These findings provide compelling evidence that the long-accepted sigma cycle does not apply to all bacteria,” Aniruddha Tewari, co-author of the study, added. “It opens new avenues for understanding bacterial gene regulation and its evolution.”

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