How does RNA unwind after transcription from DNA?
-A curious visitor from The Tech
September 25, 2009
This is a great question. As you probably know, your DNA has the instructions for making you. And that DNA has two strands stuck together -- the famous "double helix."
To "read" the information in DNA, a cell needs to pry the two strands apart. Then it reads along one strand. Sort of like opening a book and reading the lines of writing.
Of course cells don't actually read the information in DNA like we read the lines in a book. They go through a complicated set of processes called transcription and translation. We'll focus here on the first step, transcription.
Transcription is the process where a cell makes an RNA copy of a section of the DNA. The cell reads along the DNA churning out an ever longer piece of RNA. This copied RNA is what a cell uses to carry out the information in DNA. And it is very much like a strand of DNA.
Most of this RNA strand detaches by itself as the cell reads the DNA. But when the cell is done reading, there is a small bit of RNA still attached to the DNA. So what we have is a bubble in the DNA with one end of a long piece of RNA stuck to one strand of the DNA.
At least in bacteria, the DNA is set up so that when the cell is done reading, the RNA is only weakly attached to the DNA. Also, there are parts of the RNA that like each other more than they like DNA and vice versa. So the RNA ends up folding back on itself and being set free and the DNA zips back up.
All of these things work together to cause the RNA to let go. But sometimes even all of this isn't enough and the cell needs a little help.
One of these helpers in bacteria is something called Rho. Rho can help detach the last bit of RNA from the DNA.
Similar things probably happen in people, goats, fish, plants and other eukaryotes. But scientists haven't nailed down all the details like they have in bacteria. We'll have to wait and see what clever ways eukaryotes have come up with to deal with this problem.
That is the 30,000 foot level answer. To really understand all of this, we need to get a little closer to where we can see the details. Then we'll be able to see why the RNA eventually lets go.
The Key to DNA and RNA is Base Pairing
DNA has four bases, A, G, C, and T. The information we talked about before is stored in the DNA using different combinations of these letters.
These bases aren't just important for this information. They are also used to line up each DNA strand with its mate.
Basically, an A on one strand of DNA will only line up with T on the other strand. And a G will only match up with a C. This is enough to keep the right DNA strands stuck together. And enough to make an RNA copy.
This is because RNA works very similarly. It too has 4 bases -- A, G, C, and U. The U acts very much like a T but has some critical differences (see below).
So when the cell makes an RNA copy, it opens the DNA and adds the matching RNA base as it goes along. If it opens the DNA and sees a T, it puts an A in the RNA. If the next DNA letter is a G, it puts a C into the RNA. And so on until it reaches the end.
I keep saying that the cell does this and the cell does that. The cell actually has proteins that act like little machines that do everything it needs done. The protein that makes RNA copies from DNA is called RNA polymerase or RNAP.
RNAP Makes RNA Copies of DNA
RNAP is like a big machine with many different parts. The first step to making RNA from DNA is to assemble the RNAP on the DNA.
As I said before, DNA has two strands twisted together. RNAP has to unwind the two strands before it can start to read the DNA.
Once the DNA is unwound, the RNAP can begin to piece together an RNA copy. RNAP reads the base pairs of the DNA one by one and copies them into RNA. As it moves, the polymerase adds new bases to the RNA to match the sequence of the DNA.
Scientists still don't know exactly how the RNA copy unsticks from the DNA as RNAP moves along. But we can get some clues from the shape of RNAP itself. RNAP has a big groove running down its center. This is for the strand of DNA that RNAP is reading.
Next to the big groove for the DNA strand, there is a smaller groove. This groove is for the RNA copy to exit. Between the big groove and the smaller one, there's a glob of protein that looks like a wedge. This wedge might be what forces the DNA apart from the RNA strand.
So the RNA strand floats freely behind RNAP. But it is still attached to the DNA where the polymerase is adding new bases.
RNAP's shape doesn't explain how RNA lets go of DNA when it isn't moving. Scientists have studied RNA and RNAP in bacteria to figure this out.
Road Signs Tell RNAP When to Stop
There are two ways that RNA is released in bacteria. The first way is the simplest.
Remember, RNAP travels along the DNA and reads the sequence of bases. When it is time to stop making RNA, RNAP hits a "stop" sign in the DNA.
A couple of things can happen at this stop sign. The first is that part of the RNA is attracted to itself. This causes a small section of double stranded RNA called a hairpin to form. Often this makes the DNA/RNA shorter in the bubble.
The second part has to do with the stop sign itself. In bacteria, the stop sign is actually a series of A bases next to each other. When RNAP reads through the stop sign, it adds many U's to the RNA strand. Remember, U stands for Uracil, which can act like a T.
A group of these U's in the RNA paired together with A's in the DNA aren't as sticky as the other base pairs like C and G or A and T. The A's in the original strand are more attracted to the T's of the DNA than they are to the U's of RNA. So the DNA zips back together and forces the RNA out.
Letting go of the RNA is this "simple" only some of the time in bacteria and hardly ever in more complex beasts like ourselves. The rest of the time, RNAP needs a little help from other proteins to let go of the RNA and fall off the DNA.
An important helper in bacteria is the protein Rho. Scientists aren't sure how it helps separate RNA from DNA but they have some ideas.
One idea is that Rho can grab on anywhere along the RNA strand. Then Rho starts to race toward RNAP, where the RNA strand is still stuck to the DNA. Once Rho catches up, it can unwind the RNA from the DNA.
Scientists know that the simplest mechanism hardly ever works in people. Our polymerases may need lots of stop signs in a row. Or they may need helpers like Rho.
We don't know the answer yet for eukaryotes like ourselves, but scientists are working on it. One day soon, I may be able to tell you some of the ways our cells make RNA let go of DNA.
Stacey Wirt, Stanford University
A fun animation showing transcription in eukaryotes like us.