Dr. Frank Grosveld points out how little we actually know about the details of transcription and the molecular machinery involved.
Transcription Factories
We have this loop structure of the genome. And at the same time, we know that every gene that’s being transcribed, that’s active, is part of what we call transcription factories. So it’s actually in a particular spot together with other genes. So they’re localized in a particular discrete spot. A factory. And a bunch of other genes are in the next spot, and a bunch of other genes are in the next spot. And so on and so forth.
So now imagine you have a loop structure. And out of that loop structure, certain ones are coming out of that structure, and they’re now into these transcription factories. The same is true for replication for transcription factories.
…I would like to actually answer that question as to whether the DNA moves to these factories, and then actually when it’s being transcribed, moves through the factory or not.
And so if we could start to understand how that process actually works at the molecular level, that would be one of my dreams. And one of the simple questions in there is if you imagine that a gene is being transcribed, it needs a big machine– the polymerase with the associated factors– that has to go across the template.
Transcription Machinery & DNA Template: How Do They Move?
Now there’s two ways of doing it. The machine goes around the template. Or the machine sits there and the template goes through it. So a purely academic question, so to speak. So both theories exist. And I would like to actually answer that question as to whether the DNA moves to these factories, and then actually when it’s being transcribed, moves through the factory or not.
And the beginning of that question is that the initiation, the start of transcription, certainly happens in that factory. But then we already know that the next stage takes place outside that initial focus. That doesn’t mean that in the next layer, if you like, where transcription and elongation happens, where the rest of the gene is transcribed, that the template couldn’t move through the polymerase. I just don’t know at the moment.
We don’t even know– and this is all quite strange– we don’t even know when you produce the RNA– genes can be 100 KB long, some of them. Most are much shorter, but they could be that long. We have no idea where the RNA is relative to the DNA. We know that it is being spliced. So it is being processed as transcription still goes on.
And we know that that’s taking place on the outside of these foci. But we don’t actually know what it looks like. So those are very intriguing things to see what happens at that level.