A research team based at Massachusetts General Hospital (MGH) has identified 80 new genes essential to the process of RNA interference (RNAi), a powerful new research tool for inactivating genes in plants or animals.
They used the RNAi process itself to find new genes that participate in the gene-silencing mechanism, which someday may help to fight human disease. The report will appear in the journal Science and is receiving early online release on the Science Express website.
"The gene activation produced by RNAi is exquisitely specific, which gives it enormous potential for therapeutic application," says Gary Ruvkun, PhD, of the MGH Department of Molecular Biology, the study's senior author. "Imagine short, double-stranded RNA molecules that could be synthesized quickly and inexpensively to silence a single gene. Promising targets could include viruses like HIV and hepatitis C or cancer-causing oncogenes. An RNAi-based treatment for age-related macular degeneration is already in clinical trials." Ruvkun is a professor of Genetics at Harvard Medical School.
RNAi was originally identified in the C. elegans roundworm and the flowering plant Arabidopsis thaliana, both of which are common model organisms for biological research. The process interrupts the usual transfer of instructions from double-stranded DNA, through single-stranded messenger RNA and finally into proteins. Short, double-stranded pieces of RNA bind to the complementary messenger RNA segments, shutting down gene expression. RNAi occurs naturally in plants and animals and may help control resistance to viral infection, among other functions.
For the current study, lead author John Kim, PhD, and his colleagues developed a strain of C. elegans into which they added a gene that caused the worms to glow under ultraviolet light but also turned that gene off using RNAi. They then used RNAi to inactivate every one of the worms' 19,000 genes by feeding the 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.