Research Summary

Understanding the regulatory role of G-quadruplex in modulating gene expression in Mycobacterium tuberculosis (Mtb).

G-quadruplex (G4) is non-canonical secondary structure. These motifs are formed naturally in nucleic acid by sequences that are rich in G’s. Genomes of diverse organisms contain G4 motifs, which are important in regulating multiple biological functions such as transcription, genomic stability, and stress resistance. Owing to the regulatory role of G4, they are known to modulate cancer progression and other pathogenic infections such as malaria. Moreover, targeting G4 is actively under consideration for cancer therapy. Interestingly, genome of one of the most successful human pathogen Mycobacterium tuberculosis (Mtb) is 65%GC-rich. It is also known that Mtb has an unusual capacity to adapt under diverse environmental conditions by changing gene expression for its survival during infection. However, we lack clear knowledge of mechanisms responsible for coordinating gene expression under various growth conditions in Mtb. Our in-silico analysis revealed that ~ 30% of Mtb genes contain putative G4 forming motifs in their regulatory regions, indicating that G4 sequences might play an important in regulating expression. Despite this, so far there is no study on understanding the role of G4 motifs in this difficult-to-track intracellular pathogen. Therefore, our aim is to systematically dissect G4 mediated regulation in Mtb. Knowing these mechanisms will shed new light on the basic biology of Mtb and also on how this pathogen survives in response to various stress conditions. Results from such a comprehensive study will not only deepen our understanding of previously uncharacterized relation between functionally important G4 and virulence in Mtb but also open up new avenues of fundamental and translational researches, which will most likely aid in better tuberculosis management.

Figure Legend: Localization of G4 (G-quadruplex) in regulatory region and their putative biological function during replication, transcription and translation. Through the Wellcome-DBT India Alliance Early career Fellowship, we are trying to understand how G4 regulates gene expression and its effect on Mtb pathophysiology.