New Insights into the Functions of Transcription Factors that Bind the RNA Polymerase Secondary Channel.

Nikolay Zenkin,Yulia Yuzenkova

doi:10.3390/biom5031195

Abstract

Transcription elongation is regulated at several different levels, including control by various accessory transcription elongation factors. A distinct group of these factors interacts with the RNA polymerase secondary channel, an opening at the enzyme surface that leads to its active center. Despite investigation for several years, the activities and in vivo roles of some of these factors remain obscure. Here, we review the recent progress in understanding the functions of the secondary channel binding factors in bacteria. In particular, we highlight the surprising role of global regulator DksA in fidelity of RNA synthesis and the resolution of RNA polymerase traffic jams by the Gre factor. These findings indicate a potential link between transcription fidelity and collisions of the transcription and replication machineries.

Highlights

Transcription, the initial stage of gene expression, is intricately regulated
The long N-terminal coiled-coil domain protrudes through the secondary channel of RNA polymerase (RNAP), while the C-terminal globular domain is thought to be responsible for binding to RNAP
The Gre factor protrudes its coiled-coil domain through the secondary channel of RNAP, where it substitutes for the catalytic domain

Summary

Introduction

Transcription, the initial stage of gene expression, is intricately regulated. This regulation is vital for the coordination of transcription with other cellular processes and, for the successful adaptation of the cell to the environment. C-terminal domain, responsible for binding to RNAP, and a coiled-coil domain, which, at least for some of SCBFs, has been shown to be inserted through the secondary channel to modulate transcription. The genes coding for secondary channel binding factors are absent from several bacterial genera such as the cyanobacteria and several smaller groups (Aquificaceae, Dictyoglomaceae and Fusobacteriaceae) [25], suggesting that specific features of their RNAPs may compensate for the lack of SCBFs. SCBFs. The long N-terminal coiled-coil domain protrudes through the secondary channel of RNAP (see panel B), while the C-terminal globular domain is thought to be responsible for binding to RNAP. The Gre factor protrudes its coiled-coil domain through the secondary channel of RNAP, where it substitutes for the catalytic domain. Our recent results suggest that DksA may respond to binding of an incorrect NTP in the active center, and increase the accuracy of transcription (see text and Figure 2 for details) [29]. While DksA cannot prevent or resolve sequence-dependent backtracking, it increases accuracy of RNA synthesis and, reduces the chance of misincorporation and, reduces formation of one base pair backtracked pause

Gre Factors

Factors with Unknown Functions

Regulation and Competition between SCBFs

Misincorporation and Conflicts between Transcription and Replication

Conclusions