Structural dynamics of the active center of multisubunit RNA polymerases during RNA synthesis and proofreading

Abstract

Multisubunit RNA polymerases are complex molecular machines that are responsible for transcription of genes in all cellular organisms and possess several catalytic activities, the most important of which are nucleotide addition to the growing RNA chain and RNA cleavage. Efficient and accurate RNA synthesis requires switching between different RNA polymerase activities that depends on the structural state of the elongation complex and conformational dynamics of the enzyme active center. The RNA polymerase active center contains two magnesium ions, which coordinate reactive groups of substrates, an d structural elements that are involved in the binding a nd correct orientation of substrates and also participate in R NApolymerase translocation. The most important of these elements are G-loop and F-helix and also regions that affect their conformational mobility. In this review, we discussed mechanisms of structural rearrangments taking place in the activecenter of multisubuniit RNA polymerases during transcription and provided several examples of RNA polymerase regulation by factors that affect the binding of catalytic magnesium ions and conformational mobility of G-loop and F-helix.