Ancient Ways Innate Immunity in Plants, Flies, and People

The efficacy of RNAi in mammalian cells has naturally animals and is in competition with the fifth and thirteenth led to the successful demonstration that the specificity chapters on the biochemistry and enzymology of RNAi of RNAi can be exploited to inhibit dominant oncogenes as the most informative and enjoyable chapter. There while the potency of RNAi can inhibit virus replication are also well placed chapters devoted to RNase III and and function in cultured cells and mice. These observa-RNA-dependent RNA polymerase enzymology. tions bode well for effective gene-specific therapeutic The remaining chapters cover organism-specific de-applications. tails for achieving and using RNAi. There is a compre-The structural similarity between siRNAs and micro-hensive chapter on the ins and outs of whole-genome RNAs (miRNA), small single-stranded RNAs imperfectly RNAi screening using the remarkable ability to initiate complementary to their target mRNAs that repress RNAi in C. elegans by soaking them in dsRNA or feeding mRNA translation (Ambros, Cell 107, 823–826, 2001), led them bacteria that express gene-specific dsRNA. There to the finding that these two gene regulatory processes are two separate chapters on RNAi in Drosophila; one share a common dsRNA processing enzyme and associ-describing diverse strategies for exploiting RNAi in Dro-ate with homologous proteins. The similarity in plants sophila cell lines and the other in whole flies. The thir-is even more extensive as miRNAs can act by an RNAi-teenth chapter on mammalian RNAi, along with an excel-like slicing of the target mRNA rather than repressing lent comparative review of RNAi enzymology, provides translation (Llave et al. a summary of documented best practices. RNAi in avian Experiments with human cell extracts indicate that the embryos is poised to revitalize this decades old model perfect versus mismatched complementarity between for embryology and this " shocking " chapter, focused the guide RNA and the mRNA target determines whether on initiation of RNAi by electroporation of long dsRNA the mRNA is sliced or repressed, suggesting overlap in chick, causes me to wonder how truly widespread between the siRNA and miRNA-associated machinery the antiviral response in vertebrates is. introduces what I believe is the brightest future for RNAi: siRNAs and miRNAs, along with other less homogenous the use of RNAi in nontraditional model and nonmodel noncoding RNAs, are implicated in a wide-range and organisms. First, it is in the odd little creatures that growing number of RMGS phenomena including diverse unexpected phenomena like catalytic RNA, RNA …