- Tuberculosis bacteria challenge the universal σ-cycle model of gene transcription
- Findings published in Nucleic Acids Research overturn a decades-old molecular biology concept
- Insights may inform new strategies against TB and drug-resistant bacterial infections
Tuberculosis is one of the world's deadliest infectious diseases and now, a team of scientists has discovered a fundamental flaw in a long-standing model of how bacteria control gene expression that can form the base for innovative strategies to combat tuberculosis and other bacterial infections, an official statement said on Thursday. Scientists believed that a protein called ‘σ factor' binds RNA polymerase, initiates bacterial transcription and is then released once the enzyme begins elongating RNA. This process, known as the ‘σ-cycle', was assumed to be universal across bacteria, including TB bacteria.
For years, scientists believed that a protein called σ factor binds RNA polymerase, initiates bacterial transcription and is then released once the enzyme begins elongating RNA. This process, known as the σ-cycle, was assumed to be universal across bacteria, including TB bacteria.
However, a new study from Bose Institute, Kolkata, an autonomous institute of the Department of Science and Technology (DST), overturns this assumption.
Researchers Dr Jayanta Mukhopadhyay and Dr N. Hazra found that while some σ factors in M. tuberculosis dissociate from RNA polymerase during transcription, others remain firmly attached throughout the process.
Their research, published in international journal Nucleic Acids Research, reveals that a mechanism taught for decades in molecular biology textbooks — the so-called “universal σ-cycle”, does not apply to all bacteria or all regulatory proteins.
“The study focuses on tuberculosis (TB) causing bacteria, Mycobacterium tuberculosis, and shows that different σ (sigma) factors, proteins that guide RNA polymerase to specific genes, behave in strikingly different ways during transcription, the first step of gene expression,” said the Ministry of Science and Technology.
The discovery that σF remains bound to RNA polymerase suggests a so far unknown mechanism by which the bacterium ensures sustained expression of stress-response genes, an insight with important implications for TB biology.
Drug-resistant strains pose an increasing global threat to cure of the disease. M. tuberculosis (TB) bacteria survive inside the human host by precisely regulating gene expression under extreme stress conditions.
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