Prot-RAN
Financiado
What drives the RAN translation and why do we get neurodegenerative disease when...
What drives the RAN translation and why do we get neurodegenerative disease when it goes wrong?
The short tandem repeats are common in human genome, but their uncontrolled expansions may lead to several inherited disorders. In Prot-RAN project, I will focus on the expansion of trinucleotide CGG repeats (CGGexp) in the 5’UTR...
The short tandem repeats are common in human genome, but their uncontrolled expansions may lead to several inherited disorders. In Prot-RAN project, I will focus on the expansion of trinucleotide CGG repeats (CGGexp) in the 5’UTR of fragile X mental retardation 1 (FMR1) gene, which causes common neurodegenerative disease, known as fragile X-associated tremor/ataxia syndrome (FXTAS). The pathogenesis of FXTAS remains unclear, and one of the possible mechanisms, the repeat associated non-AUG initiated (RAN) translation, can be shared in majority of microsatellite expansion diseases, as it was already linked to 9 different disorders. In FXTAS, the CGGexp enhances RAN translation from the 5’UTR of FMR1 mRNA, what leads to the production of toxic polyglycine or polyalanine containing proteins. These aberrant products accumulate in nuclear inclusions in the brain of FXTAS patients, impairing the nuclear lamina architecture and leading to neuronal death. The RAN translation mechanism is still not well understood; therefore, in the proposed project I will identify and investigate the role of proteins implicated in RAN translation initiation/elongation. To achieve this goal, I will benefit from the synergy between my long-time experience in mass spectrometry and the expertise of the host lab in RNA biology, and I will bridge cutting-edge proteomics with RNA biology techniques. Briefly, I will employ the CGGexp RNA-targeting pull-down approaches combined with proteomic profiling, RNA mutagenesis, high throughput protein expression analysis and RNA/protein interaction studies in a context of their functional implications. The role of identified proteins will be then verified in other expansion disorders, e.g. Huntington’s disease, giving insight into more global view of the RAN translation. As a result, the discovered factors driving RAN translation and knowledge of mechanism of their action could be used as potential new targets for therapeutic strategies.
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Duración del proyecto: 35 meses
Fecha Inicio: 2020-04-03
Fecha Fin: 2023-03-24
Fecha Fin: 2023-03-24
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2023-03-24
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
WF-02-2019:
Widening Fellowships
Cerrada
hace 5 años
Presupuesto
El presupuesto total del proyecto asciende a
150K€
Líder del proyecto
UNIWERSYTET IM. ADAMA MICKIEWICZA WPOZNANIU
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
169.66K€ |
Participante