Research Interests

Our research program integrates structural biology, biophysics, and biochemistry to map the structural adaptations and thermodynamic mechanisms governing post-transcriptional gene regulation across higher eukaryotes. We have revealed a conserved mechanism by which proteins containing multiple copies of a domain, such as the dsRNA-binding domain (dsRBD) containing proteins, modulate interdomain linker orientation and dynamics to select a prominent dsRNA binder while recruiting other domains for auxiliary functions. We have also elucidated dsRBD fold modifications that drive heterodimeric complex formation, regulate Dicer-mediated processing of endogenous inverted-repeat dsRNA, and steer epigenetic gene regulation in vascular plants. Furthermore, we explore macromolecular liquid-liquid phase separation as an antiviral defense countermeasure, detailing how canonical folds in host surveillance proteins adopt characteristic structural extensions that redistribute surface charges, triggering weak, multivalent self-association that drives the assembly of dsRNA-dependent gel-like condensates to physically stall viral replication complexes. Notably, our study shows that lowly populated, invisible, dynamically exchanging excited states, rather than ground-state structures alone, play a crucial role in molecular recognition. Using structurally identical proteins, our study highlights that lowly populated excited-state conformations enable flexible proteins to recognize structurally dynamic viral dsRNAs, whereas rigid counterparts interact only with rigid RNA. We also determined the de novo high-resolution solution structure of CRC (~32 kDa), representing the largest NMR-driven high-resolution solution structure solved in India, and revealed non-canonical RNA binding and the dynamic interplay among Crc, CrcY/Z RNA, and Hfq:Crc:mRNA in regulating carbon catabolite repression in bacteria. Overall, our work demonstrates that structural adaptations and conformational plasticity in RNA-binding proteins enable organisms, from bacteria to higher eukaryotes, to tailor RNA-induced gene-regulatory responses.

Selected Publications

1. Condensate Formation by Structured dsRNA Binding Domains Drives RNA Sequestration in Plants.
   Jaydeep Paul, Debadutta Patra, Preeti C. Behera, Supriti Das, Upasana Rai, and Mandar V. Deshmukh
   Journal of the American Chemical Society, 2026, Epub ahead of print. doi: 10.1021/jacs.6c05034.
2. Conformational plasticity in dsRNA binding domains drives functional divergence in RNA recognition.
   Debadutta Patra, Jaydeep Paul, Upasana Rai, Aravind P. S., and Mandar V. Deshmukh
   Journal of the American Chemical Society, 2025, 147, 17088-17100. doi: 10.1021/jacs.5c02057.
3. The mechanism of DRB7.2:DRB4 mediated sequestering of endogenous inverted-repeat dsRNA precursors in plants.
   Sneha Paturi, Debadutta Patra, Priti Chanda Behera, Ramdas Aute, Nilam Waghela, Priyadarshan Kinatukara, and Mandar V. Deshmukh
   eLife, 2025, 14, RP105762. doi: 10.7554/eLife.105762.
4. DRB4 dsRBD1 drives dsRNA recognition in Arabidopsis thaliana tasi/siRNA pathway.
   C. Sai Chaitanya, Ramdas Aute, Upasana Rai, and Mandar V. Deshmukh
   Nucleic Acids Research, 2017, 45, 8551-8563. doi: 10.1093/nar/gkx481.
5. Structure of RDE-4 dsRBDs and mutational studies provide insights in the dsRNA recognition in C. elegans RNAi.
   C. Sai Chaitanya and Mandar V. Deshmukh
   Biochemical Journal, 2014, 458, 119-130. doi: 10.1042/BJ20131347.