Indian Scientists Rewrite 50-Year-Old Biological Principle on Gene Regulation

A team of Indian and international scientists has overturned a central dogma of molecular biology by challenging a 50-year-old textbook model of bacterial gene regulation. The groundbreaking discovery reshapes our understanding of how bacteria control their genes—an insight with far-reaching implications for microbiology, antibiotic development, and synthetic biology.

For decades, biology textbooks have taught the “sigma (σ) cycle” model, which describes how σ factors help RNA polymerase bind DNA to begin transcription and then detach during the elongation phase. This model, built primarily on observations of E. coli σ70, has long been believed to be universal across bacterial species.

However, new research by scientists from the Bose Institute, an autonomous institute under the Department of Science and Technology (DST), and Rutgers University, USA, reveals that this long-accepted cycle does not apply to all bacteria.

The study, published in the prestigious journal PNAS (Proceedings of the National Academy of Sciences), shows that in Bacillus subtilis, the principal initiation factor σA remains attached to RNA polymerase throughout the transcription process, instead of being released after initiation. A modified form of E. coli σ70, which lacks region 1.1, also stays bound—contradicting previous scientific assumptions.

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

Using a powerful combination of advanced biochemical assays, chromatin immunoprecipitation, and fluorescence imaging techniques, the researchers monitored sigma factor behavior in real time. They discovered that the traditional σ cycle does not function the same way across all microbes.

“These findings clearly demonstrate that the long-accepted σ cycle does not apply to all bacteria,” noted co-author Aniruddha Tewari. “This opens up exciting new directions for understanding bacterial evolution and regulatory mechanisms.”

Broader Impact

The discovery has significant implications:

• Antibiotic Development:
  Understanding species-specific transcription mechanisms can help design targeted antibiotics or transcription inhibitors to prevent bacterial infection.

• Microbial Biotechnology:
  Manipulating transcription factors can help engineers design microbes that produce biofuels, biodegradable plastics, pharmaceuticals, and other valuable compounds more efficiently.

• Microbial Physiology & Stress Response:
  The findings shed new light on how bacteria react to stress and adapt to challenging environments.

The research team includes Shreya Sengupta, Soumya Mukherjee, and Nilanjana Hazra from Bose Institute, and Yon W. Ebright and Richard H. Ebright from Rutgers University.

The full study is available at: doi:10.1073/pnas.2503801122