SACKI · Cross-kingdom investigation of the mammalian retroviral silencing suppressor Tas to identify novel silencing factors
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2006-09-30 → 2008-09-29
- EU contribution
- €149,670
- Participants
- 1
- Scheme
- EIF
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Results in brief
Final Activity Report Summary - SACKI (Cross-kingdom investigation of the mammalian retroviral silencing suppressor Tas to identify novel silencing factors)
All cells in an organism have exactly the same genes; they contain exactly the same DNA. They are, however, very different. For example, cells that make up an eye have completely different properties from those in the liver. The cells are different, because different genes in them are active. Therefore, processes that allow genes to be switched on and off in different cells are key to understand how organisms work at the cellular level. When a gene is active, it is being copied from DNA into a similar molecule called RNA. RNA is the template for synthesis of a protein whose structure is specified by the gene. The content of proteins gives cells their different properties. For example, specific proteins in the eye sense the light, while other specific proteins in our liver detoxify the alcohol consumed on a happy Friday night. The copying machines that produce the RNA gene copies (messenger RNAs or mRNAs) and the final protein products are important targets of gene regulation. Somewhat surprisingly, a large group of RNA molecules has recently emerged as components of such regulation. These RNA regulators are 20 to several hundred fold smaller than mRNAs, and are, because of their tiny size, simply called small RNAs. Small RNAs were discovered in 1999, and we are only starting to understand how the cells generate these molecules and use them to regulate genes. Studying the plant Arabidopsis thaliana - the equivalent of the fruit fly for genetic research on plants - our research focuses on how small RNAs regulate genes. The prevailing idea has been that these small RNAs work fundamentally different in plants and animals, such that they destabilise mRNAs in plants, but repress the efficiency with which they produce protein in animals without degrading mRNAs. We have found that plant small RNAs not only affect the quantity of mRNAs, but also their ability to be read by the protein synthesis machines. We have identified several factors important for this process, some of which have turned out to have counterparts in animals. This has opened up venues to study and understand common elements of small RNA based gene regulation in animals and plants.
Data: CORDIS, © European Union
Project objective
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.
Original text from CORDIS.
Participants
- CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE · PARISCoordinatorFrance
Links
Data: CORDIS, © European Union