Project description
Argonaute proteins and sRNA pathways
Small RNAs (sRNAs) serve as major players in a multitude of pathways, controlling development and preserving genome integrity in plants and animals. To perform their biological function, sRNAs are loaded to Argonaute (AGO) proteins, and the AGO/sRNA complexes recognise and regulate the target genes. The EU-funded AGOras project proposes a series of experimental approaches to study the transport routes and subcellular localisation and roles of AGO–sRNA complexes. Researchers plan to combine cell biology, RNA biochemistry, protein modelling, bioinformatics, deep-sequencing analyses, nuclear fractionation methods and single-molecule studies to identify key subcellular localisation signals of AGO proteins, elucidate AGO shuttling mechanisms and define the cytoplasmic and nuclear roles of AGO proteins in RNA pathways.
Objective
Small RNAs (sRNA) have emerged as major players in a multitude of pathways, controlling development and preserving genome integrity in plant and animals. To fulfill their biological function, sRNA are loaded into ARGONAUTE (AGO) proteins, together this AGO/sRNA complex recognizes and regulates the target genes. Depending on the organism and the sRNA pathway involved, AGOs have nuclear and/or the cytoplasmic localization and functions. Although globally AGO mediated processes are reasonably understood, the transport routes involved, their shuttling regulation and transient subcellular roles remain completely unknown. This proposal outlines a series of mutually reinforcing experiments to mechanistically study the transport routes and subcellular roles of AGO-sRNA complexes. In details, combining cell biology, RNA biochemistry, protein modeling, bioinformatics, deep-sequencing analyses, nuclear fractionation methods and single-molecule studies the proposed project aims to: 1) Identify key subcellular localization signals of AGO proteins; 2) Decipher AGO shuttling mechanism and their regulation; and 3) Dissect cytoplasmic and nuclear roles of AGO proteins on RNA pathways. The anticipated results will provide a crucial breakthrough in the eukaryotic RNA pathways and gene regulation fields. The interest in non-coding RNA action goes beyond mere mechanistic knowledge. Understanding non-coding RNA action is of paramount importance given the extraordinary potential held by the therapeutic, veterinary and agronomic exploitation of these molecules. As a result, the knowledge on the transport routes and subcellular roles of AGO-sRNA complexes obtained during the proposed project will provide an important contribution to European excellence and competitiveness in the field.
Fields of science
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Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
08193 Cerdanyola Del Valles
Spain