Genetic Requirements for Inheritance of RNAi in C. elegans

Abstract

In Caenorhabditis elegans, the introduction of double-stranded RNA triggers sequence-specific genetic interference (RNAi) that is transmitted to offspring. The inheritance properties associated with this phenomenon were examined. Transmission of the interference effect occurred through a dominant extragenic agent. The wild-type activities of the RNAi pathway genes rde-1 and rde-4 were required for the formation of this interfering agent but were not needed for interference thereafter. In contrast, the rde-2 and mut-7 genes were required downstream for interference. These findings provide evidence for germ line transmission of an extragenic sequence-specific silencing factor and implicate rde-1 and rde-4 in the formation of the inherited agent.

Guest list or black list: heritable small RNAs as immunogenic memories

“…While in most cases wild-type gene activity is restored to baseline after dsRNA exposure in the second generation, targeting certain genes can result in lasting interference [16]. Several factors influence the persistency of RNAi inheritance, and segregation of the effect does not follow Mendel's rules of heredity -I will now briefly describe the dynamics of this unusual genetic process.…”

“…In C.elegans RNAi is inherited as a dominant factor [16] in both the oocyte and the sperm, and the silencing can be more persistent when transmitted through the male germline [17]. This is suppressing since the sperm's volume is less than 1% of the volume of oocyte.…”

“…Stable RNAi-mediated methylation of DNA cannot explain inheritance seen in worms, since in C.elegans cytosine methylation does not seem to occur [20] suggesting alternative RNAi inheritance mechanisms are utilized as well. Indeed, unlike epigenetic effects which are mediated by DNA modifications, heritable RNAi effects were shown to propagate to the next generation of worms as a diffusible epigenetic element (demonstrated using animals in which deletions were introduced to remove the target DNA), suggesting that in C.elegans the chromosomal locus is either redundant or dispensable for transmission of transgenerational memory [16,17,21]. Recent evidence in worms suggests, however, that RNAi inheritance can involve a nuclear RNAi mechanism and chromatin remodeling genes as well [22].…”

“…This observation challenges an important principle in evolutionary biology known as the "Weismann Barrier" (also termed "The second law of biology"), according to which genetic information cannot pass from the soma to the germline [13]. Recently it was demonstrated that higher organisms also use RNAi to silence genes in a non-cell autonomous manner [14,15], suggesting that soma-germline RNA-mediated communication could be widely conserved.While in most cases wild-type gene activity is restored to baseline after dsRNA exposure in the second generation, targeting certain genes can result in lasting interference [16]. Several factors influence the persistency of RNAi inheritance, and segregation of the effect does not follow Mendel's rules of heredity -I will now briefly describe the dynamics of this unusual genetic process.…”

“…Several factors influence the persistency of RNAi inheritance, and segregation of the effect does not follow Mendel's rules of heredity -I will now briefly describe the dynamics of this unusual genetic process. In C.elegans RNAi is inherited as a dominant factor [16] in both the oocyte and the sperm, and the silencing can be more persistent when transmitted through the male germline [17]. This is suppressing since the sperm's volume is less than 1% of the volume of oocyte.…”