Nuclear Structure and Function Research Group

Overview
Textbooks tell us that RNA polymerases track like locomotives along their templates, and little about the ways genomes are organized.
We suggest:
• active polymerases do not track (they are fixed to the sub-structure, and reel in their templates as they extrude their transcripts; a review),
• genomes are organized into loops by clusters of engaged polymerases (a review), and
• promoter-factory distance determines how frequently a gene is transcribed (a review; another review).

A working model for transcription by RNA polymerase II. When genes strung along a template are transcribed, active polymerases aggregate into clusters to loop intervening DNA.  We call a cluster a transcription 'factory' as it contains several polymerizing complexes and transcription units. Each factory is then surrounded by a 'cloud' of loops. Only one loop with two transcription units is shown attached to a factory: • on the left, through one unit and an engaged polymerase (transcription has just initiated, and the transcript is just beginning to emerge), • on the right, through a cluster of transcription factors (for the sake of convenience, this attachment is shown – incorrectly – to be stable, but it is repeatedly broken and remade). Another polymerase and a tetrameric '200S' particle are shown docked on the surface of the factory. Clustering ensures there is a high local concentration of polymerases in the factory, so few (if any) transcripts are made elsewhere. Press Start: • the polymerase (left) reels in its template, as it extrudes its transcript (which is packaged into the 200S particle), • the other promoter diffuses through the nucleoplasm and collides with a polymerase in the factory, transcription begins, and the transcript is incorporated into the 200S particle, • on termination, transcription units and polymerases detach and the 200S particle diffuses away (Iborra et al., 1998;  2000). Go to a higher-power view of one polymerizing complex in a factory.

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