Indian scientists have helped rewrite a foundational principle of molecular biology, overturning a 50 year old textbook model of bacterial gene regulation and opening new possibilities for antibiotic development and synthetic biology.
In a study published in the Proceedings of the National Academy of Sciences, researchers from the Bose Institute, an autonomous institute under the Department of Science and Technology, in collaboration with Rutgers University, have demonstrated that a central concept known as the sigma cycle is not universal across bacteria.
For nearly five decades, biology textbooks have described how bacteria initiate gene expression through the sigma cycle. According to this widely accepted model, sigma factors bind to RNA polymerase to initiate transcription and then dissociate to allow elongation of the RNA chain. This concept was largely based on observations of the Escherichia coli sigma 70 factor.
The new research challenges this long standing view. The team found that in Bacillus subtilis, the principal transcription initiation factor sigma A remains bound to RNA polymerase throughout the entire transcription process rather than being released after initiation. They also observed that a modified version of Escherichia coli sigma 70 lacking a region known as 1.1 similarly remains attached during transcription.
Jayanta Mukhopadhyay, corresponding author from the Bose Institute, said the findings fundamentally change the understanding of bacterial transcription and gene regulation. He noted that in Bacillus subtilis, sigma A stays attached to RNA polymerase throughout transcription, contradicting the classical sigma cycle model.
The researchers used a combination of advanced biochemical assays, chromatin immunoprecipitation and fluorescence based imaging to monitor the behaviour of sigma factors in real time. Their experiments showed that Bacillus subtilis sigma A and the truncated Escherichia coli sigma 70 variant remain stably associated with transcription complexes. In contrast, full length Escherichia coli sigma 70 is released stochastically during elongation.
Aniruddha Tewari of the Bose Institute, a co author of the study, said the findings provide compelling evidence that the long accepted sigma cycle does not apply to all bacteria. He added that the discovery opens new avenues for understanding bacterial gene regulation and its evolutionary pathways.
The study was authored by Aniruddha Tewary, Shreya Sengupta, Soumya Mukherjee and Nilanjana Hazra from the Bose Institute, along with Y W E, R H E, Yon W Ebright, Richard H Ebright and Jayanta Mukhopadhyay from Rutgers University, United States.
The discovery has broad implications for microbiology and biotechnology. By refining the understanding of transcription mechanisms in bacteria, the research may contribute to the design of more effective antibiotics or regulatory inhibitors that block infection mechanisms. It may also support the engineering of microorganisms capable of producing biofuels, biodegradable plastics and therapeutic compounds more efficiently.
The findings mark a significant contribution by Indian scientists to global biological research and underscore the importance of revisiting established scientific doctrines in the light of new evidence.
