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

Objectif

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.

Champ scientifique (EuroSciVoc)

Mots‑clés

Programme(s)

Thème(s)

Régime de financement

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

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Appel à propositions

(s’ouvre dans une nouvelle fenêtre) HORIZON-MSCA-2022-PF-01

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Coordinateur

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Contribution nette de l'UE
€ 209 620,88
Adresse
Meyerhofstrasse 1
69117 Heidelberg
Allemagne
Région
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Type d’activité
Research Organisations
Liens
Coût total
Aucune donnée