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Cross-kingdom investigation of the mammalian retroviral silencing suppressor Tas to identify novel silencing factors


RNA silencing is a fundamental process controlling gene expression in eukaryotes. Although a set of core proteins that initiate and execute RNA silencing have been identified, the complexity of the pathways involved suggests that additional components are yet to be discovered. In particular, negative regulatory pathways of RNA silencing remain poorly understood, although evidence for their existence has recently emerged. Such pathways are likely to be recruited by viral suppressors of silencing.

The goal of the project is to unravel novel silencing factors conserved across kingdoms and to characterize their function paying particular attention to involvement in negative regulatory pathways. We will exploit our recent finding that the mammalian retroviral suppressor of silencing Tas is functional in both human cells and plants. A combination of genetic, functional genomic and biochemical tools will be used to identify host proteins that are targeted by Tas in both Arabidopsis and human cells. Their implication in the various silencing pathways will then be investigated.

For example, the plant system will be exploited for its amenability to forward genetic analysis by screening directly for mutations in host genes that alleviate silencing suppression conferred by Tas. Likewise, the conserved function of Tas across kingdoms allows powerful filtering of functional genomics data obtained in both systems, facilitating identification of host targets relevant to RNA silencing pathways.

Altogether, this project will illuminate key aspects of the biology of RNA silencing and open new avenues to further investigation of this important research field.

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