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Newly identified mechanism for silencing genes points to possible anti-cancer strategies

thway, one that led us to a mechanism that blocks the cellular machinery that produces protein from messenger RNA."

In earlier studies, Shiekhattar identified a three-molecule complex known as RISC and showed that it plays a vital role in generating microRNAs. In the current study, Shiekhattar and his colleagues extended those studies to find that RISC also interacts with another complex that includes molecules required to build functional ribosomes. Ribosomes are cellular organelles responsible for translating messenger RNA into protein. Closer investigation showed that the new complex also included a component called eIF6. This molecule is known to interfere with the proper assembly of ribosomes, which prevents them from doing the work of translating messenger RNA into protein.

"We wondered if certain microRNA-responsive genes might be attracting microRNAs that then recruited eIF6 to that location," Shiekhattar says. "If so, the eIF6 would prevent the assembly of a competent ribosome, thus blocking messenger RNA translation at that gene. The result would be to silence that specific gene. We tested this idea in human cells and in worms and found it to be the case in both. Interestingly, this not only supported our hypothesis, but to see it in such different organisms also suggested that the mechanism involved has long been conserved in evolution."


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Contact: Franklin Hoke
hoke@wistar.org
215-898-3716
The Wistar Institute
16-May-2007


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