CHAPTER 2: Molecular Basis for Transcriptional Fidelity Control by RNA Polymerase II

RNA polymerase II (Pol II) is a key enzyme for gene expression and exhibits a high fidelity in copying DNA sequence into an RNA chain (1 mistake in 10⁴–10⁶ nucleotides). In this chapter, we will summarize recent efforts to dissect the molecular mechanism of transcriptional fidelity control. In particular, we will focus on elucidation of the structural basis of three key fidelity checkpoint steps. We also summarize a synthetic nucleic-acid chemistry approach that complements canonical genetic and biochemical approaches. These chemical tools allow us to understand how individual chemical interactions and intrinsic structural features of nucleic acids are specifically recognized by Pol II and utilized for fidelity control.