1、RNnomics Advanced MCB Presentation Series I,Group Members: 孙群, 刘军, 段文霞，刘少英,RNA Silencing: The Genomes Immune System Science, 2002, Vol. 296:1263-1265,Ronald H. A. PlasterkHubrecht Laboratory, Center for Biomedical Genetics, 3584 CT Utrecht, Netherlands,Genomes Immune System,Genomes are database sens
2、itive to invasion by viruses: 45% of the human genome consists of remnants of previous transposon/virus invasions and elementsA defense mechanism conserved among eukaryotes with two characteristics:Specificity against foreign elementsAbility to amplify and raise a massive response against an invadin
3、g nucleic acid.,Vertebrate Immune System,Use a two-Step strategy: A large repertoire of antibody-encoding genes is generated from a limited set of gene segments by combinatorial gene rearrangementsThis repertoire is stored in a distributed fashion over large numbers of cellsClonal selection and expa
4、nsion of specific cells results in an immune response specifically directed to the immunogen.,How to Protect the integrity of the genome,How to recognize self from nonselfHow to amplify an initial response in a specific fashionAnimal models: Nematodes, Flies, C. elegans,Ways of Genomes Immune Respon
5、se,Selective methylation of transposon sequences in the genome An RNA-based silencing mechanism: ancient core mechanism, conserved among species from different kingdoms (fungi, animals, and plants) likely acts as the immune system of the genome.,Function of RNA Silencing,Protect against viruses and
6、transposonsPosttranscriptional gene silencing (PTGS) and virus-induced gene silencingdsRNA: not normally encountered in high concentration, exogenous dsRNA can trigger gene silencing RNAi: genomes “immune system” with the systemic effect, can be induced by feeding,Fig. 1. A model for the molecular s
7、teps in RNA silencing.,Fig. 1. A model for the molecular steps in RNA silencing.,Self and Nonself,Transponsons or viruses induce dsRNA: corresponds to their own sequence:Both strands are transcripted dsRNATerminal inverted repeats of transposon can result in snap-back dsRNASome other sensor of the f
8、oreign transposons,Amplification,Small amounts of dsRNA are able to silence a vast excess of target mRNA in C. elegansThe Dicer enzyme cuts long dsRNA molecules into short primary siRNAs. Each siRNA can potentially target a homologous mRNA, this provides a level of amplification A catalytic mechanis
9、m, in which siRNAs are used multiple times, can provide further amplification.,Target-Dependent Amplification,Short RNAs can serve as primers on target mRNA and subsequent generation of secondary siRNAs initiate an RNA-directed RNA polymerization reaction 1st step: mRNA is recognized by primary siRN
10、As. dsRNA is cut into short siRNAs, presumably these are converted from dsRNA into ssRNA, 2nd step: after the antisense siRNA has base paired to the target mRNA, target-directed amplification can occur polarity in some species,Conclusion,The gene immune system recognizes molecular parasites, raises
11、an initial response, stabilizes and amplifies this response. Parts of the RNAi-silencing machinery is of conservationRNAi silencing refers to a family of mechanisms that are quite different in context and detail. Almost certainly be the case for more specific aspects of the biology: systemic RNAi in C.elegans, spreading of silencing in plants, and suppression of silencing induced by several plant viruses.,Thank You!,
