A Vicious Cycle: RNA Silencing and DNA Methylation in Plants

Abstract

If RNA silencing evolved as a host defense mechanism against RNA viruses, why would a DNA component be built into the system? The DNA component could perhaps guard against reverse-transcribed viral segments that find their way into the host genome. In this scenario, the invading sequence could potentially insert downstream of an endogenous promoter and continue to exert deleterious effects even in the absence of the original infecting virus. However, because the system is designed so that the invading sequence is efficiently marked with methylation by viral RNAs, its continued expression from an upstream endogenous promoter would lead to aberrant transcripts, siRNA production, and RNA silencing. An additional benefit in this situation is that the preexisting viral siRNAs generated from the integrated viral sequence could “immunize” the host plant against reinfection with the same virus. With increasing plant genomic sequence resources, it might be possible to identify integrated viral segments and obtain experimental support for this hypothesis.Whether animal RNA silencing systems also trigger methylation and chromatin changes remains ambiguous. Some of the best-characterized animal systems, such as nematode worms, lack genomic methylation machineries, so a direct comparison with plant RNA silencing-induced methylation changes cannot be made. And even animals like mice that do have genomic methylation lack the ability to efficiently propagate the non-CG methylation pattterns associated with RNA silencing in plants. Superficially, these methylation differences suggest that RNA-directed DNA methylation might be unique to plants. In this case, animals might have evolved a different mechanism for marking integrated RNA virus segments, or they might have dispensed with this silencing reinforcement mechanism entirely. However, because the underlying chromatin changes associated with RNA-directed methylation in plants are currently unknown, it could be that animals make the same chromatin changes in response to RNA silencing despite differences in methylation patterning. In fact, the possibility of RNA-silencing-associated chromatin changes in nematode worms is suggested by the observation that some mutations that block RNA silencing also activate the movement of previously encrypted transposable elements (Ketting et al., 1999xKetting, R.F., Haverkamp, T.H.A., van Luenen, H.G.A.M., and Plasterk, R.H.A. Cell. 1999; 99: 133–141Abstract | Full Text | Full Text PDF | PubMed | Scopus (530)See all References(Ketting et al., 1999). Clearly, an exciting and challenging direction for the field is dissecting the factors that associate with genomic targets of RNA silencing in both plants and animals. Perhaps RNA-directed methylation in plants is pointing us toward a new layer of genome defense against invasive sequences.