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Researchers design a tool to induce controlled suicide in human cells
Date:12/17/2009

How to interfere with protein production?

Cells are bags full of proteins and all proteins are formed by large chains of amino acids. Cells continually make these molecules through a highly complex system. One of the components involved in protein production, a process in which the Gene Translation Lab is specialized, is transfer RNA (tRNA). The function of tRNA is to transport the protein synthesis machinery and the precise amino acids required for each protein under construction. Geslain designed new tRNAs, very similar to natural ones, but that place erroneous amino acids into the protein sequences under construction. "When these tRNAs are introduced, the cells starts to make and accumulate defective proteins and it reacts in response. Given that the cell still conserves the healthy proteins present before the introduction of our tRNA, we can observe the extent to which the healthy part can correct the problem. We can also see when these defects are no longer correctible and how and when cells enter the suicide programme."

The researchers know which modification they introduce into the protein synthesis system and can measure the cellular responses to the error produced. More serious mutations can trigger cell suicide in less than 48 hours, while less severe ones allow the cell to survive for 5 days. "Thus we can observe the whole spectra of cell responses triggered and measure when they begin and the connections between them. Finally, by means of transcriptomics studies, we can identify new components involved in this process", explains Ribas.

The lab has started to obtain results using this new tool. Analyses indicate that part of the cell response to the accumulation of misfolded proteins is the production of several micro-RNAs, small molecules that regulate gene expression. "We still don't know what they do or what genes they repress but we are discovering very surprising functional connections", notes the IRB Barcelona
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Contact: Snia Armengou
sonia.armengou@irbbarcelona.org
34-934-037-255
Institute for Research in Biomedicine (IRB Barcelona)
Source:Eurekalert

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