RNA polymerases I, II, and III

A small workshop might have one all-purpose worker; a big factory hires specialists. Bacteria run all transcription with a single RNA polymerase, but eukaryotic cells, with their far larger and busier genomes, divide the work among three distinct RNA polymerases. Knowing who makes what is a quick way to organize the messy variety of RNA in a cell.

The three nuclear polymerases each have their own products and locations. RNA polymerase I works in the nucleolus and makes the large ribosomal RNA precursor — the bulk of the ribosome's RNA, and by mass most of the RNA a cell makes. RNA polymerase II makes all the messenger RNAs (the templates for proteins) plus many regulatory RNAs (such as microRNA precursors and long noncoding RNAs); it is the most regulated and the one served by the TATA box, general transcription factors, and Mediator. RNA polymerase III makes a set of small, abundant RNAs — transfer RNAs, the small 5S ribosomal RNA, and other little helpers. They are all close relatives built on the same core design, but each reads its own kind of promoter. A handy way to remember: I and III build the protein-making infrastructure (rRNA and tRNA), while II copies the genes that carry actual coded messages.

This division explains some otherwise puzzling facts. It is why a drug or toxin can hit one class of RNA selectively — the deadly mushroom toxin alpha-amanitin, for instance, potently blocks Pol II while barely touching Pol I, which is why it shuts down messenger-RNA production and is so lethal. It also reflects priorities: ribosomal RNA must be made in enormous quantities, so it gets its own dedicated polymerase and its own subcompartment, the nucleolus.