Gene Expression: (Part 1) Transcription in Eukaryotes

Have you ever baked cookies? Ok, so that’s a dumb question. But how about this one — did you use a cookbook? Unless you’re one of a seriously small percentage of humans with a photographic memory, then chances are that you did. So, making cookies was a 2 step process: writing the information down and deciphering that information into a different language.

I know it’s corny, but just go with it… for the sake of education.

From that awful analogy, have you figured out that there are 2 separate forces at work here? There’s the information-writing party and the information-reading party. In your case, the cookbook writers were… oh, you get it.

So, lets take what we now know and apply it to cell biology. In THAT case, the information-writing party would be anything involved in transcription, and the information-reading party would be anything involved in translation. Since this particular article is supposed to be about transcription, let’s go into a little more detail, but always keep in mind that everything in this process is about writing information down so that it can be read later.

Think of the genome as a library, full of cookbooks. This entire library is in the DNA language, and the ribosomes (the information-reading party) don’t speak DNA. There’s a wealth of information there for making all kinds of proteins, but the ribosomes just can’t read it, so it’s necessary that the information be translated into RNA, the ribosome’s native language.

The obvious place to start is in the nucleus at the gene of interest. We know from my post on the parts of a gene that there is a part called the promoter. I’ve heard the promoter referred to as everything from an on/off switch to an airport landing strip, and they all make sense. The promoter is the part of the gene that says “HEY! Bake THIS recipe!!”

There is a specific word in the DNA language that transcription factors, proteins that do speak DNA, understand as meaning “park here.” We refer to this word as a sequence called the TATA box. These transcription factors (there are many of them that work together to start transcription) act as a pit crew for RNA Polymerase. Their job is to find the starting line, get the RNA Pol in the right spot, and then give it any starting push that it may need (from stored energy, like ATP).

The RNA Polymerase is the only enzyme that is actually bilingual. Once it is given the proper push by the transcription factors, it glides along the DNA template strand, reading the DNA words and translating them into RNA. The two languages are very similar, in fact that only difference is that whereas the DNA alphabet is A, G, C, and T, the RNA alphabet is A, G, C, and U.

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At this point in the process, we have RNA sliding down the DNA template strand translating the directions from DNA into RNA. So, what next? There must be something programmed into the system to stop it at the end. Nope. In fact, transcripts don’t even make it to the end 100% of the time.

The RNA Polymerase glides along the top of the DNA strand in much the same way as a kid running down the curb on a street. It doesn’t take much force to knock the kid off the curb, and it takes even less to knock the RNA Pol off the DNA. There are no strong magnetic forces acting that hold the RNA in place, and the enzyme itself fits over the DNA like a horseshoe on a string. Sometimes, the transcript lasts all the way to the end of the coding sequence, sometimes it doesn’t, and sometimes it may go on for many thousands of base pairs after the gene has ended. Obviously, though, enough transcripts last until the end of the coding region, or else this system wouldn’t work.

You would think that, logically, as soon as the RNA Pol falls off the template strand, the new mRNA molecule would be finished and the process would be over. However, grammar is always important. I’m sure you can think of a few instances in which bad grammar made something hard to read, or even completely unreadable. Cells use a type of grammar as well, but we call it “post-transcriptional mRNA modification.” I know it’s a big scary term, but it simply means that after the RNA Pol does its job, the cell changes the molecule a little bit.

This modification consists of three very important parts: A 5′ cap, 3′ polyadenylation, and intron excision. These are all rather simple as well, but terms can be scary. When I say 5′ cap, I mean that the cell contains a host of enzymes that add a protective molecule onto the transcript at the 5′ end that signals the ribosomes to do their job later as well as protects the transcript from being sliced up by exonuclease enzymes. The 3′ polyadenylation, which means “lots of Adenosines on the 3′ end,” also protects the mRNA from exonuclease shredding. Intron excision, however, it probably the most important. In this process, chunks of DNA words that don’t actually mean anything are taken out of the directions in the mRNA.

Why these stinkin things are even there, we don’t know, but we DO know that if they aren’t taken out of the mRNA transcript, there will be no cookies later on. You see, in the DNA language, it is customary to take chunks of sentences and overlap them with each other. In order to read the original sentence, we must remove the chunks of other sentences. We call the original sentence chunks “exons” because we want to EXPRESS them, and the INTERVENING sentence chunks are called “introns.”

Once the cell has written down the recipe in a language that the ribosomes can understand and put it in the correct grammatical format, then the mRNA transcript can leave the nucleus and move on to the second step in protein expression.

The Short Version

1. DNA attacked by Transcription Factors that recognize the TATA box
2. RNA Polymerase binds to Transcription Factor complex, then begins to synthesize mRNA strand complementary to the DNA template
3. 5′ Capping, 3′ Poly-A tail, Intron Excision
4. Move out of Nucleus

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Best of Luck,

Grey