Scientist Uncovers Switch Controlling Protein Production

[steven johnson]

ScienceDaily (Dec. 23, 2010) — A scientist from the Florida campus of The Scripps Research Institute has discovered a molecular switch that controls the synthesis of ribosomes. Ribosomes are the large machineries inside all living cells that produce proteins, the basic working units of any cell. These new findings offer a novel target for potential treatments for a range of diseases, including cancer.

The study identified the molecular switch, essentially formed by a small sequence of RNA, that controls a critical part of ribosome synthesis to allow for strict, albeit temporary, regulation of the process.

"These kinds of switches in RNA are thought to be slow acting," said Katrin Karbstein, an assistant professor in the Department of Cancer Biology at Scripps Florida who helped lead the study. "That suggests a point where we might intervene to modify the process -- then you could potentially shut down the pathway, because if you don't produce ribosomes, you cannot make proteins. Thus, cells can't grow. That would be a desirable outcome in cancer, for example."

"While we believe that this switch is essential for ribosome assembly, it seems unlikely that this is the only event that regulates cleavage," Karbstein said. "However, tight regulation of ribosome synthesis is essential to ensure the structural integrity of mature ribosomes."

"What is interesting," Karbstein said, "is that as the organism becomes more complex, the number of cleavages needed increases. This may make the process more accurate and that may be an evolutionary advantage, but even in bacteria this cutting is not done in a simple way. We still don't know exactly why that is."

Perhaps these strictly ordered cleavage steps are introduced to produce singularly perfect intermediates, she added. This is important because cleavage is an irreversible energy-releasing process with the potential to shift the landscape of assembly towards the final product. As a result, cleavage steps should be carefully controlled and should only occur if the assembly intermediate is correct.

"Ribosomes make mistakes rarely, on the order of one in 10,000 amino acid changes," Karbstein said. "A lot of this accuracy depends on conversations between different parts of the ribosomes, so if the structure of the RNA isn't correct, these conversations can't happen. And that means more mistakes, and that's not good because it can lead to any number of disease states."

Scientist Uncovers Switch Controlling Protein Production
>