RNA polymerase and Mechanism of Transcription
RNA polymerase is the enzyme that carries out the first step in gene expression, synthesis of RNA. We study RNA polymerase catalytic mechanism with emphasis on translocation, a step specific to processive polymerases and motor enzymes.
RNA polymerase (RNAP) is the enzyme that carries out the first step in gene expression, synthesis of RNA. All cellular RNAPs are multisubunit enzymes sharing homologous catalytic cores totaling ~2,500 amino acids. During RNA synthesis RNAP functions as a molecular motor and a helicase; its movement along the DNA is ultimately powered by the free energy liberated as nucleoside triphosphates are condensed into the nascent RNA and pyrophosphate is released. By importance and conservation among the life kingdoms RNAP rivals the ribosome, yet is considerably less complex and is amenable to kinetics and mechanistic studies in well-defined in vitro systems.
We study RNAP catalytic mechanism with emphasis on translocation, a step specific to processive polymerases and motor enzymes. Utilizing a relatively simple bacterial RNAP system we address mechanical, kinetic and energetic aspects of RNAP movement along the DNA. Another related line of our research deals with transcription elongation factors. Understanding the means by which transcription factors modulate RNAP catalytic efficiency and translocation kinetics helps us to unravel the basic mechanism of this complex molecular machine. Finally, RNAP is both an excellent phylogenetic marker for inferring species phylogenies and an attractive paradigm for studying the protein evolution. We employ molecular phylogenetic analyses to study the evolution of protein landscape in catalytically important areas of RNAP, as well as the evolution of other transcription-related proteins and the whole organisms.