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Projekt
Function of the Ubiquitin-Like Protein Hub1
Antragsteller
Professor Dr. Stefan Jentsch (†)
Fachliche Zuordnung
Zellbiologie
Förderung
Förderung von 2008 bis 2014
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 71697671
Hub1 is a highly conserved ubiquitin-like protein, which consists solely of the ubiquitin fold. Unlike canonical ubiquitin-like modifiers, Hub1 interacts with proteins only non-covalently. Genetic studies have suggested a role of Hub1 in RNA splicing, but its precise function remained poorly defined. We found that Hub1 binds to an element termed HIND, which is present in certain spliceosomal proteins (Snu66 or Prp38). The X-ray structure of a Hub1-HIND complex revealed a novel mode of interaction. Binding of Hub1 alters the spliceosome but barely affects general splicing. However, Hub1-modified spliceosomes gain the ability to recognize non-canonical 5’-splice sites. In yeast, SRC1 is alternatively spliced via two non-canonical 5’-splice sites, and this requires Hub1-modified spliceosomes. Interestingly, Hub1 functions regardless whether it binds to an HIND element on Snu66 or Prp38, or even when fused linearly to these splicing proteins. Thus Hub1 does not modulate its direct target, but rather affects the spliceosome in general. We plan to conduct genetic screens to identify components that affect Hub1-dependent splicesite selection positively or negatively. As Hub1, Snu66 and HINDs are highly conserved, we will also ask whether Hub1’s function is conserved. We identified residues on Hub1 that are crucial for splicing or for its essential role for cell viability, and thus we will search for the crucial binding partners. In addition to a full description of the function of Hub1, we expect that the proposed research will also provide general insights into the mechanisms of ubiquitin-like proteins and how they influence protein activities.
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