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Elucidation of the evolution of post-transcriptional regulation by characterizing the cnidarian microRNA pathway

Projektbeschreibung

Evolution kleiner RNS bei alten Tieren

Kleine RNS-Moleküle sind eine Klasse nichtcodierender RNS-Moleküle mit etwa 20 bis 30 Nukleinbasen, die an verschiedenen zellulären und physiologischen Prozessen einschließlich der Genregulation beteiligt sind. MicroRNA (miRNA) sind die am besten untersuchte Klasse kleiner RNS in bilateralen Arten wie Insekten, Nematoden und Wirbeltieren. Das vom Europäischen Forschungsrat finanzierte Projekt CNIDARIAMICRORNA untersucht kleine miRNA in nicht-bilateralen Arten wie der Seeanemone Nematostella vectensis, einer Verwandten von Korallen und Quallen. Die Projektergebnisse zeigen, dass die miRNA von Nematostella den miRNA von Pflanzen in Bezug auf ihre Wirkungsweise ähneln. Durch den Einsatz fortschrittlicher biochemischer und genetischer Methoden werden die Forschenden einen Einblick in die Biogenese und Wirkung kleiner RNS in der Seeanemone geben und die Evolution und die alten Formen dieses wichtigen molekularen Signalwegs beleuchten.

Ziel

Over the past decade small RNAs such as microRNAs (miRNAs) and small interfering RNAs (siRNAs) have been shown to carry pivotal roles in post-transcriptional regulation and genome protection and to play an important part in various physiological processes in animals. miRNAs can be found in a very wide range of animals yet their functions were studied almost exclusively in members of the Bilateria such as insects, nematodes and vertebrates. Hence studying their function in representatives of non-bilaterian phyla such as Cnidaria (sea anemones, corals, hydras and jellyfish) is crucial for understanding the evolution of miRNAs in animals and can provide important insights into their roles in the ancient ancestor of Cnidaria and Bilateria. The sea anemone Nematostella vectensis is an excellent model for such a study since it can be grown in large numbers throughout its life cycle in the lab and because well-established genetic manipulation techniques are available for this species. Our preliminary results indicate that miRNAs in Nematostella frequently have a nearly perfect match to their messenger RNA (mRNA) targets, resulting in cleavage of the target. This mode of action is common for plant miRNAs, but is very rare in Bilateria. This finding together with my recent discovery of a Nematostella homolog of HYL1, a protein involved in miRNA biogenesis in plants, raises the exciting possibility that the miRNA pathway existed in the common ancestor of plants and animals. Here I suggest to bring together an array of advanced biochemical and genetic methods such as gene knockdown, transgenesis, high throughput sequencing and immunoprecipitation in order to obtain - for the first time - a deep understanding of the biogenesis and mechanism of action of small RNAs in Cnidaria. This will provide a novel way to understand the evolution of this important molecular pathway and to evaluate its age and ancestral form.

Finanzierungsplan

ERC-STG - Starting Grant

Gastgebende Einrichtung

THE HEBREW UNIVERSITY OF JERUSALEM
Netto-EU-Beitrag
€ 1 499 587,00
Adresse
EDMOND J SAFRA CAMPUS GIVAT RAM
91904 Jerusalem
Israel

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Aktivitätstyp
Higher or Secondary Education Establishments
Links
Gesamtkosten
€ 1 499 587,00

Begünstigte (1)