DNA-directed RNA polymerase complex (RNAP)

The DNA-directed RNA polymerase complex is a multi-subunit molecular machine essential for the first step of gene expression, where it catalyzes the synthesis of RNA from a DNA template (Saecker et al., 2017, PubMed). In bacteria, the core enzyme (α2ββ'ω) associates with a sigma factor to form the holoenzyme, which recognizes specific promoter sequences to initiate transcription (Browning & Busby, 2016, Nature Reviews Microbiology). This complex is a primary target for several classes of antibiotics, most notably the rifamycins, which bind to the β-subunit and physically obstruct the path of the growing RNA chain, leading to the termination of transcription (Campbell et al., 2001, Cell). In eukaryotic cells, three distinct versions of the complex (RNA Polymerase I, II, and III) are responsible for synthesizing different types of RNA, and their dysregulation is a hallmark of many cancers where increased transcriptional activity supports rapid cell growth (Khanna & Weinmann, 2013, Nature Reviews Genetics). Because of its central role in life, the complex is highly conserved, yet structural differences between bacterial and eukaryotic versions allow for the development of selective inhibitors that minimize host toxicity (Ma et al., 2016, Chemical Reviews). Therapeutic challenges include the rapid emergence of resistance through point mutations in the polymerase subunits and the need to avoid off-target effects on mitochondrial transcription (Arnold et al., 2012, PLOS Biology).

Other names

RNA polymerase–DNA transcription complexTranscription elongation complexRNAP-DNA complexRNA polymerase holoenzymeDNA-dependent RNA polymerase

Inhibition of RNA synthesis by binding to polymerase subunits to sterically block RNA elongation or prevent promoter clearance.