The molecular architecture of a protein complex that helps determine the fate of human cells has been imaged for the first time by researchers with the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab). Known as a human RISC-loading complex, this structure consists of snippets of ribonucleic acid (RNA) that control whether genetic messages are silenced or expressed.From these new images, the research team, led by biochemist Jennifer Doudna and biophysicist Eva Nogales, has been able to propose a model of how RISC and other so-called “small RNA molecules” are able to target specific messenger RNA molecules for gene silencing and/or destruction. Their results have been published in the journal Nature Structure and Molecular Biology in a paper entitled: “Structural insights into RNA Processing by the Human RISC-Loading Complex.” RISC stands for RNA-Induced Silencing Complex. Doudna and Nogales both hold joint appointments with Berkeley Lab, the University of California (UC) Berkeley, and the Howard Hughes Medical Institute (HHMI). Co-authoring the paper with them were Hong-Wei Wang, Cameron Noland, Bunpote Siridechadilok, David Taylor, Enbo Ma and Karin Felderer. “We now know how the three main components of the RISC machinery - the Dicer and Argonaute enzymes and the TRBP binding protein - are arranged, and how they interact with one another and are likely to interact as a complex with messenger RNA,” says Doudna, an authority on RNA molecular structures. “Our work should help others in the design of mutants to test the mechanisms of the RNA binding and processing used by the gene-silencing RNA machinery in humans.”
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