Indian scientists, in collaboration with researchers from Rutgers University, have challenged a fundamental biological concept that has shaped textbook understanding of bacterial gene regulation for nearly five decades. Their findings could open new possibilities for developing antibiotics and studying bacterial evolution.
For years, biology textbooks have described the “sigma cycle,” a model based primarily on Escherichia coli σ70, which suggested that sigma factors bind to RNA polymerase to initiate transcription and then detach once the process begins. The new study, however, shows this model is not universal.
Researchers from the Bose Institute – an autonomous institute under the Department of Science and Technology – and Rutgers University reported in Proceedings of the National Academy of Sciences (PNAS) that the principal sigma factor in Bacillus subtilis, known as σA, stays attached to RNA polymerase throughout transcription rather than being released after initiation. A modified version of E. coli σ70 showed similar behaviour.
“Our work shows that in Bacillus subtilis, the σA factor stays attached to RNA polymerase all the way through the transcription process,” said Dr. Jayanta Mukhopadhyay of the Bose Institute. “This fundamentally changes how we think about bacterial transcription and gene regulation.”
The team used biochemical assays, chromatin immunoprecipitation and fluorescence imaging to track the sigma factor’s behaviour in real time. They found that Bacillus subtilis σA and an E. coli σ70 variant lacking region 1.1 remain stable throughout transcription, unlike the full-length E. coli σ70, which detaches unpredictably during elongation.
“These findings provide compelling evidence that the long-accepted sigma cycle does not apply to all bacteria,” said co-author Aniruddha Tewari. “It opens new avenues for understanding bacterial gene regulation and its evolution.”
The discovery has wide-ranging implications, as gene regulation plays a central role in how bacteria respond to stress, cause infections and interact with their environment. The research could support new strategies for antibiotic development by targeting previously unknown aspects of bacterial transcription.
The study also has potential applications in synthetic biology, where engineered microbes are used to produce biofuels, biodegradable materials and pharmaceuticals.
The research team included Shreya Sengupta, Soumya Mukherjee and Nilanjana Hazra from the Bose Institute, along with Yon W. Ebright and Richard H. Ebright from Rutgers University.