Dynamics based Recognition Mechanism of dsRBD-dsRNA Interaction - Harshad Paithankar - Bog

RNA performs a broad range of vital cellular functions. They serve as information carriers, form part of ribosome, exhibit catalytic activities, involved in gene regulation, etc. Most of these functions involve the interaction of RNAs with proteins. For example, the genetic information contained in DNA is transcribed to RNA assisted by RNA polymerase, the ribosome contains tRNA molecules bound to aminoacyl-tRNA synthetase that are responsible for the translation of information encoded in the mRNA, etc.. Another example of protein-RNA interaction involves the processing of RNAs by ribonucleases that form the ribonucleoprotein complex (RNP). These complexes are involved in gene regulation, antiviral defense, immune response, etc. The formation of the correct complex is governed by the different types of interactions between the amino acids of the protein and the nucleobases or ribose sugar or phosphodiester backbone of the RNA that include hydrogen bonding, electrostatic, stacking interactions, etc. Any irregularities in these interactions can lead to dysfunction of the complex and can lead to diseases such as cancer, cardiovascular dysfunction, neurodegenerative diseases, to name a few. Regardless of the large number functionally significant protein-RNA interactions known, the molecular mechanisms of interactions between the RNA and the protein are poorly understood. An important aspect of understanding these mechanisms involves the characterization of these interactions at structural, kinetic, and thermodynamic levels.

RNA molecules can fold into a variety of secondary and tertiary structures that are formed due to the various type of base-pairing interactions between the nucleobases. The base-pairing in RNA can vary from most commonly observed Watson-Crick pairs to others like Hoogsteen, Wobble, reverse Watson-Crick, reverse Hoogsteen, etc1. Proteins can recognize RNAs by interacting with a single- stranded RNA and/or secondary and tertiary structures like an RNA duplex, duplex with internal bulge or mismatch, stem-loop structures, quadruplexes, etc.