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Synthesis and Function of Non-Canonical RNA Fragments

Cel

RNA lies at the core of the central dogma of molecular biology. It can both store genetic information and catalyse biochemical reactions. An often-overlooked property is that it contains next to A, G, C, and U, approximately 170 different non-canonical nucleosides. Transfer RNAs (tRNAs), as the central adaptor molecules for translating, harbour the highest number of these non-canonical nucleosides.
A recent surprising discovery revealed that tRNAs are cleaved by, in part, unknown RNases into smaller fragments, referred to as tsRNAs, which keep the non-canonical nucleosides. The functions of this entirely novel class of RNA molecules remain unknown.
Our first goal is to prepare phosphoramidite building blocks for non-canonical nucleosides and to synthesize tsRNAs. Although all available knowledge about tsRNAs has been obtained using synthetic RNAs that lack modified nucleosides, the data suggest that their primary function is to stimulate the immune system to enhance for example anticancer responses. Consequently, we plan to focus our synthetic efforts at evaluating the immunological effects of tsRNAs. This aim is further supported by the seminal discovery of Weissman and Kariko, who demonstrated that the presence of non-canonical nucleosides, such as pseudouridine, in mRNA profoundly modulates immune recognition.
The second goal of the study is to employ the synthetic tsRNAs, containing the respective embedded non-canonical nucleosides, to investigate how these fragments are processed by specific RNases. We will analyse how tsRNAs, or their secondary cleavage products, activate immune responses. Furthermore, we plan to identify and characterize the enzymes involved in these processing pathways. Finally, we will study tsRNAs derived from pathogenic bacteria following infection, focusing on those carrying pathogen-specific non-canonical nucleosides. We hypothesize that these structures will elicit particularly strong immune responses.

Dziedzina nauki (EuroSciVoc)

Projekt nie został jeszcze sklasyfikowany według klasyfikacji EuroSciVoc.
Wskaż dziedziny nauki, które twoim zdaniem są najbardziej istotne z punktu widzenia tego projektu i pomóż nam usprawnić naszą usługę klasyfikacji.

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System finansowania

HORIZON-ERC - HORIZON ERC Grants

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Zaproszenie do składania wniosków

(odnośnik otworzy się w nowym oknie) ERC-2025-ADG

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Instytucja przyjmująca

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Wkład UE netto
€ 2 499 812,00
Adres
GESCHWISTER SCHOLL PLATZ 1
80539 Planegg
Niemcy
Region
Bayern Oberbayern München, Kreisfreie Stadt
Rodzaj działalności
Higher or Secondary Education Establishments
Linki
Koszt całkowity
Brak danych

Beneficjenci (1)