Structural and chemical perspectives of RNA polymerase II transcriptional fidelity (939.5)

Abstract

Maintaining a high transcriptional fidelity is essential to life. A long‐standing key question has been how RNA polymerase II (Pol II) recognizes DNA template and substrate and achieves such a high transcriptional fidelity. Here we use a combined structural, computational, and chemical biology approaches to gain novel insights of the molecular basis and chemical interactions in controlling Pol II transcriptional fidelity. We focused on the three key checkpoint steps in controlling transcriptional fidelity: specific nucleotide selection and incorporation, differentiation of RNA transcript extension of a matched over mismatched 3’‐RNA terminus, and preferential removal of misincorporated nucleotides from the 3’‐RNA end (proofreading). Our recent work on the systematic evaluations of individual chemical interactions and the roles of sugar integrity in controlling Pol II transcriptional fidelity will be discussed.Grant Funding Source: NIH GM085136, NIH GM102362