RNA Polymerase and Transcription Initiation

The enzyme that synthesises RNA and the carefully controlled first step in which it locates a gene, melts the DNA, and begins making a transcript.

Definition

RNA polymerase is the multi-subunit enzyme that catalyses DNA-templated RNA synthesis; transcription initiation is the regulated set of steps by which the polymerase, with appropriate factors, recognises a promoter, opens the DNA duplex, and begins synthesising RNA at the start site.

Scope

This topic covers the structure and catalytic action of RNA polymerases and the events of initiation: promoter recognition, formation of the closed and then open complex, abortive initiation, and the transition to productive elongation. It contrasts bacterial single-polymerase initiation with the multi-polymerase, factor-dependent initiation of eukaryotes. Promoter sequences and regulatory transcription factors are treated more fully in a companion topic.

Core questions

• What is the structure of RNA polymerase and how does it catalyse synthesis?
• How does the enzyme recognise where a gene begins?
• What happens when the closed promoter complex converts to an open complex?
• How does initiation differ between bacteria and eukaryotes?

Key theories

Open-complex formation

Productive initiation requires the polymerase to melt a short stretch of promoter DNA, forming an open complex in which the template strand is exposed in the active site so the first nucleotides can be joined.

Factor-guided promoter selection

Bacterial polymerase uses an exchangeable sigma factor to choose promoters, while eukaryotic polymerases depend on assemblies of general transcription factors, giving initiation its specificity and a key point of control.

Mechanisms

The core polymerase, which carries the catalytic centre, associates with an initiation factor (a sigma factor in bacteria; general transcription factors in eukaryotes) to recognise the promoter and form a closed complex. The duplex is then melted to an open complex exposing the template strand. The enzyme begins joining nucleotides, often releasing several short abortive transcripts, until it escapes the promoter, sheds initiation factors, and enters processive elongation.

Clinical relevance

Bacterial RNA polymerase is the target of important antibiotics, and eukaryotic initiation factors are implicated in disease and are studied as drug targets; presented as significance, not clinical advice.

History

RNA polymerase was identified in the early 1960s; the discovery of multiple eukaryotic polymerases and their general transcription factors, and later high-resolution structures of the enzyme caught in the act of initiation, established the mechanistic picture used in current texts.

Key figures

• Roger Kornberg
• Robert Roeder

Seminal works

• watson2013
• lodish2016

Frequently asked questions

Does RNA polymerase need a primer?

No. Unlike DNA polymerases, RNA polymerase can start a new strand from scratch on the template, so transcription does not require a primer.

What is a sigma factor?

A bacterial initiation subunit that directs the core polymerase to specific promoters; different sigma factors let a cell transcribe different sets of genes.