transcription initiation

Before a copyist can start writing, they have to find the right page and put pen to paper at the first word. Transcription initiation is exactly this: RNA polymerase locating the start of a gene, opening the DNA there, and committing to the first few letters of RNA. It is the most decisive of the three stages, because getting started is where most regulation happens — the cell controls a gene chiefly by controlling whether transcription begins at all.

In bacteria, initiation goes like this. The RNA polymerase holoenzyme (core enzyme plus a sigma factor) scans the DNA until the sigma factor recognizes a promoter, the gene's start signal. The enzyme binds there forming a 'closed complex', then melts open about a dozen base pairs to expose the template — the 'open complex', also called the transcription bubble. With the template strand exposed at the start site, the polymerase begins joining the first nucleotides into RNA, usually starting with a purine. In eukaryotes the same goal is reached more elaborately: a crowd of general transcription factors assembles on the promoter and recruits RNA polymerase II into a pre-initiation complex, and only then does synthesis begin.

Initiation isn't a clean one-shot event. The polymerase often stutters at the very start, making and releasing short useless transcripts — this is abortive initiation — before it succeeds in clearing the promoter and switching into productive elongation. Because so much is decided here, initiation is the principal lever of gene control: activators and repressors, sigma factors, and transcription factors all act largely by speeding up or blocking this step.