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Scientists identify genetic pathways essential to RNA interference

worms bacteria that produce double-stranded RNA for each gene. Inactivation of about 90 genes caused the worms to glow, indicating that those genes were essential to the RNAi process that had been suppressing expression of the fluorescence gene.

Some of the identified genes ?many of which have human counterparts ?code for proteins involved with the packaging and processing of RNA, but others may be involved with the regulation of DNA itself, including the repair of DNA damage. "These new steps indicate there is more to RNAi than RNA destruction," says Kim. "And the connection to DNA damage pathways, which was totally unexpected, suggests a potential connection between RNAi and the control of cell division in cancer."

The researchers note that better understanding the mechanisms underlying RNAi could help transform what has been a research tool into a powerful therapeutic tool. Although the process has worked well in studies of cultured human cells, it has not yet been effective for experimentally suppressing gene expression in living mammals. Identifying each step in the RNAi process could lead to more successful inactivation of disease-related genes. And in addition to the technique's potential for gene silencing, controlling levels of RNAi that may underlie some cancers or be used in viral replication may offer further clinical potential.

Along with Kim, the study's co-first authors are Harrison Gabel and Ravi Kamath, MD, PhD, of the MGH Department of Molecular Biology. Additional authors are Michael Dybbs and Joshua Kaplan, PhD, of MGH; Muneesh Tewari, MD, PhD, Jean-Francois Rual, Nicolas Bertin, and Marc Vidal, PhD, of Dana-Farber Cancer Institute; Amy Pasquinelli, PhD, of the University of California at San Diego; and Scott Kennedy, PhD, of the University of Wisconsin.


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Source:Massachusetts General Hospital


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