Thursday, 16 June 2011

Stepping over the stop

Imagine you have a robot that is baking a cake according to a precisely written recipe. And when it finishes making the cake base, the recipe says “stop here”, even though there are instructions for a creamy topic below. Cells do a similar thing: in an RNA molecule they have a recipe for a protein molecule, and they follow the instructions exactly, until they reach a ‘stop’ word. A recent finding by Karijolich and Yu (1) has shown that, at least in yeast cells, there are enzymes that can change the “stop” instruction and make the cells read it as continuation of the protein and keep reading the instructions further. It’s as if you erased the “stop here” instruction from the recipe and gave it back to the robot. After making the base it would go straight to making the topping.
Why would the cells do that? Sometimes they might need the protein to be bigger, because the extra bit can provide extra functions. For instance it can cope better in stressful conditions. In normal circumstances, introduction of such an extra bit would be a waste of energy. But when the environment changes from normal to stressful, the cells don’t need to produce a whole range of new protein-coding RNAs, they already have them, and all they need to do is change “stop” to “go on” and voila! A new protein that copes well with environmental stress. And it needn’t be stress, there can be plenty other things that can change inside or outside of the cell, and having such RNA molecules is quite a fast way of responding to these changes. It’s like you just found out that your friends are bringing kids to the dinner party and the kids just loooove creamy topping. You don’t need to prepare a whole new set of instruction for your robot to follow, you just remove the “end here” bit and a cake with creamy topping is on the way.
In the publication I’m mentioning here, the experiments were done in yeast. But it’s a well known fact that plenty of the processes that go on in yeast cell also happen in higher organisms – including humans. What implications has it got? In this publication, the cells were discovered to edit the “stop” instruction in the RNA molecule, but it is very likely that other bits of the instruction might be altered as well. This might lead to substantial change in how we understand the relation between instructions in RNA and what protein we expect to be made from these instructions.

1. Converting nonsense codons into sense codons by targeted pseudouridylation

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