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Encapsulated eukaryotic ribosome assembly

The production of fully functional ribosomes is vital for every cell, with failure causing human diseases called ribosomopathies. Eukaryotic ribosome assembly is catalyzed by ~200 assembly factors that guarantee efficient and accu... ver más

31/08/2022

UHEI

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

RUPRECHTKARLSUNIVERSITAET HEIDELBERG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Ver 2 Participantes

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2022-08-31

Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:

ERC-2016-ADG: ERC Advanced Grant

I+D

Cerrada hace 8 años

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2 Participantes

UHEI

2.00M€ | Lider

INNOVACIONES MICROELECTRONIC...

296.28K€ | Participante

Últimas noticias

29-11-2024: IDAE En las últimas 48 horas el Organismo IDAE ha otorgado 4 concesiones

29-11-2024: ECE En las últimas 48 horas el Organismo ECE ha otorgado 2 concesiones

29-11-2024: CMVAMADRID En las últimas 48 horas el Organismo CMVAMADRID ha otorgado 37 concesiones

Duración del proyecto: 62 meses Fecha Inicio: 2017-06-30
Fecha Fin: 2022-08-31

Líder del proyecto

RUPRECHTKARLSUNIVERSITAET HEIDELBERG

TRL 4-5

Presupuesto del proyecto 2M€

Descripción del proyecto The production of fully functional ribosomes is vital for every cell, with failure causing human diseases called ribosomopathies. Eukaryotic ribosome assembly is catalyzed by ~200 assembly factors that guarantee efficient and accurate production of ribosomal subunits along a temporally and spatially ordered pathway. About one third of these factors are utilized in the formation of the earliest biogenesis intermediate, termed 90S pre-ribosome or small subunit processome. Recent insight into the 90S structure from a eukaryotic thermophile, Chaetomium thermophilum, has provided a first spatial impression on this most sophisticated process, which includes co-transcriptional RNA folding and processing, and incorporation of ribosomal proteins. Our key discovery was that the nascent ribosomal RNA, which if linear would form a long thread, is co-transcriptionally mounted into a mold formed by a highly interconnected RNA-protein scaffold on the 90S pre-ribosome. This finding raises a novel concept in RNA biology that nascent RNA folds and matures in a protected environment, which is reminiscent of protein folding that can also occur in folding chambers. I plan to challenge the idea that the 90S particle indeed encapsulates the RNA transiently, in order to protect it from unproductive interactions, allowing stepwise folding and maturation in a cascade of interdependent reactions and the involvement of energy-consuming enzymes. The groundbreaking aim of this proposal is to decipher how these processes occur in an encapsulated environment, using C. thermophilum as a model organism. This high-risk project will depend on the successful establishment of novel assays that recapitulate eukaryotic ribosome assembly in vitro, exploiting the thermostable nature of the 90S pre-ribosome. Mechanistic insight into ribosome biogenesis will lead to a better understanding of how this multifaceted process is linked to other key cellular pathways and development of diseases including cancer.

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