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Twin molecular scissors link creation of microRNAs with gene-silencing

specific messenger RNA to be inactivated. Using complementarity to match the guide miRNA to a particular length of its target messenger RNA, Dicer and TRBP then hand over the messenger RNA for cutting by Argonaute 2. Still holding the guide miRNA, RISC then scouts for additional copies of its target messenger RNA to cut. The cutting destroys the messenger RNA, effectively silencing the gene from which it was transcribed.

"The two enzymes in the complex are like two scissors working together in a concerted fashion, connected and coordinated by the third member of the complex," Shiekhattar explains.

Another scientific question surrounding RISC was also resolved by the current study. Some investigators had theorized that the activity of RISC required ATP for energy. ATP, or adenosine triphosphate, is a molecule used to store and release energy for tasks throughout the body.

"The work of RISC is being accomplished with no energy requirement whatsoever," Shiekhattar says. "All of the activity the separation of the strands, the multiple cutting steps, everything is being done in the absence of any energy use."

Instead, he says, the different molecules involved have stronger and weaker affinities for each other that govern their stepwise associations and disassociations as the process unfolds.


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Contact: Franklin Hoke
hoke@wistar.org
215-898-3716
The Wistar Institute
3-Nov-2005


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