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  Dynamic protein-protein interaction wiring of the human spliceosome.

Hegele, A., Kamburov, A., Großmann, A., Sourlis, C., Wowro, S. J., Weimann, M., et al. (2012). Dynamic protein-protein interaction wiring of the human spliceosome. Molecular Cell, 45(4), 567-580. doi:10.1016/j.molcel.2011.12.034.

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 Creators:
Hegele, A., Author
Kamburov, A.1, Author           
Großmann, Arndt2, Author           
Sourlis, C., Author
Wowro, S. J.3, Author           
Weimann, M.4, Author           
Will, C. L.5, Author           
Pena, V.6, Author           
Lührmann, R.5, Author           
Stelzel, U.2, Author           
Affiliations:
1Bioinformatics (Ralf Herwig), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479648              
2Molecular Interaction Networks (Ulrich Stelzl), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479660              
3Nutrigenomics and Gene Regulation (Sascha Sauer), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479662              
4Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433554              
5Department of Cellular Biochemistry, MPI for biophysical chemistry, Max Planck Society, ou_578576              
6Research Group of Macromolecular Crystallography, MPI for Biophysical Chemistry, Max Planck Society, ou_2035293              

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 Abstract: More than 200 proteins copurify with spliceosomes, the compositionally dynamic RNPs catalyzing pre-mRNA splicing. To better understand protein - protein interactions governing splicing, we systematically investigated interactions between human spliceosomal proteins. A comprehensive Y2H interaction matrix screen generated a protein interaction map comprising 632 interactions between 196 proteins. Among these, 242 interactions were found between spliceosomal core proteins and largely validated by coimmunoprecipitation. To reveal dynamic changes in protein interactions, we integrated spliceosomal complex purification information with our interaction data and performed link clustering. These data, together with interaction competition experiments, suggest that during step 1 of splicing, hPRP8 interactions with SF3b proteins are replaced by hSLU7, positioning this second step factor close to the active site, and that the DEAH-box helicases hPRP2 and hPRP16 cooperate through ordered interactions with GPKOW. Our data provide extensive information about the spliceosomal protein interaction network and its dynamics.

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Language(s): eng - English
 Dates: 2012-02-24
 Publication Status: Issued
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.molcel.2011.12.034
 Degree: -

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Title: Molecular Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 45 (4) Sequence Number: - Start / End Page: 567 - 580 Identifier: ISSN: 1097-2765
CoNE: https://pure.mpg.de/cone/journals/resource/954925610929