The Hidden City

Hong Kong Street at night UCLARodent at English Wikipedia [CC BY-SA 2.5 (

Picture a hidden city, that though it cannot be seen, is everywhere. Sound crazy? It’s real. And it is the most antic, madcap, crowded yet fantastically efficient city you could ever picture. It’s like Hong Kong sped up to an almost unimaginably manic pace, with all kinds of independent, apparently purposeful activities going on — fast, fast, fast! — conducted by a huge cast of actors (enzymes and other intricately sophisticated molecular machines made of proteins) that go about their business as if it were their business. There, I gave it away. This mysterious city I write about is a microscopic cell, made of DNA, RNA, proteins, and membrane. No doubt you were taught to think of a cell more or less statically, but it is a highly dynamic ever changing entity. How is all this activity coordinated and directed? The answer remains largely mysterious, and the more we find out the more the mystery grows.

We do know this much. The nucleus is where DNA, the cell’s information storage system, resides. It serves as the cell’s Grand Central Library, where a good deal of the coordination takes place. DNA, the chief orchestrator, looks like a tangled mess, but it isn’t, it’s quite organized. It has to be. Supercoiled DNA packs tightly against the nuclear wall, inactive. Nearer the center, active chromosomes stake out territories, so that in the center, their unwound loops of DNA can partner with others in an intricate dance. Clouds of signal molecules surround these loops, looking for binding sites near genes. Most genes have multiple binding sites near them. When occupied, the binding sites send signals— yes, no, no, yes, yes   — that get integrated into one overall signal. When it adds up to yes! a cascade of events begins — another kind of binding protein sits down on the DNA like a rider in a saddle, right in front of the gene, and attracts other proteins to itself, one by one. Then the cluster attracts a wandering machine called an RNA polymerase, which will copy (transcribe) the DNA into RNA. The whole complex waits like a race horse in the starting gate until the signal is given, then bang! the polymerase whizzes off, transcribing DNA into RNA at an astonishing clip of 30 nucleotides per second.

Sometimes the polymerase jumps between strands, forming an RNA made from two separate chromosomes. Sometimes polymerases racing in opposite directions run into each other, like Keystone cops. And sometimes polymerases run into what are called replication forks, the places where DNA is being duplicated in order for the cell to divide. The RNA polymerase politely steps aside.

You are probably wondering what the RNA is good for.  It gets processed and shipped out to the cytoplasm, where it is turned into proteins like the polymerase and binding proteins, or the thousands of other proteins the cell requires. Proteins are the actors that accomplish things in the cell, and the building blocks from which things are made. You will meet other examples as we go.

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