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Structural basis of human U4atac/U6atac•U5 tri-snRNP assembly

Objetivo

Minor spliceosome is responsible for the removal of a rare class of introns that are present in many essential genes. Despite its fundamental importance, much information remains elusive for a comprehensive understanding of minor spliceosome assembly and the molecular basis of the diseases associated with its malfunctions in human. In this proposal, I will investigate the assembly process of U4atac/U6atac•U5 tri-snRNP (minor tri-snRNP) by isolating relevant complexes from human cells and determining their structures using cryo-electron microscopy (cryo-EM). The U4atac/U6atac•U5 tri-snRNP is the largest pre-assembled building block of the minor spliceosome. By applying cryo-EM and proteomics, we will reveal the spatial organization and composition of the minor tri-snRNP, while the structures of its assembly intermediates will shed light on the role of assembly chaperones in the tri-snRNP maturation. Consequently, these findings will provide clues as to how minor spliceosome assembles to achieve its complex function.

Recent advances in the field of cryo-EM have opened up the possibility to study large and dynamic spliceosomal complexes at a molecular level. With our lab’s expertise in pre-mRNA splicing, cryo-EM and mammalian cell culture, we are perfectly positioned to exploit these new technologies to gain mechanistic insights into the assembly of the minor spliceosome.

Ámbito científico (EuroSciVoc)

Palabras clave

Programa(s)

Tema(s)

Régimen de financiación

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Convocatoria de propuestas

(se abrirá en una nueva ventana) HORIZON-MSCA-2022-PF-01

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Coordinador

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Aportación neta de la UEn
€ 209 620,88
Dirección
Meyerhofstrasse 1
69117 Heidelberg
Alemania
Región
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Tipo de actividad
Research Organisations
Enlaces
Coste total
Sin datos