[자연과학]2006노벨생리학상요약

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The discovery of RNA interference

In their Nature paper, Fire and Mello tested the phenotypic effect of RNA injected into the worm C. elegans. They established that annealed sense/antisense RNA, but neither antisense nor sense RNA alone, caused the predicted phenotype. Furthermore, only injection of double-stranded RNA (dsRNA) led to an efficient loss of the target mRNA. The main results can be summed up as follows: First, silencing was triggered efficiently by injected dsRNA, but weakly or not at all by sense or antisense single-stranded RNAs. Second, silencing was specific for an mRNA homologous to the dsRNA; other mRNAs were unaffected. Third, the dsRNA had to correspond to the mature mRNA sequence; neither intron nor promoter sequences triggered a response. This indicated a posttranscriptional, presumably cytoplasmic mechanism. Fourth, the targeted mRNA disappeared suggesting that it was degraded. Fifth, only a few dsRNA molecules per cell were sufficient to accomplish full silencing. This indicated that the dsRNA was amplified and/or acted catalytically rather than stoichiometrically. Sixth, the dsRNA effect could spread between tissues and even to the progeny, suggesting a transmission of the effect between cells. Furthermore, Fire and Mello made the remark that RNAi could provide an explanation for a phenomenon studied in plants for several years: posttranscriptional gene silencing (PTGS). Finally, they ended their paper by speculating about the possibility that

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