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  Structural basis for dual roles of Aar2p in U5 snRNP assembly.

Weber, G., Cristao, V. F., Santos, K. F., Mozaffari-Jovin, S., Heroven, A. C., Holton, N., et al. (2013). Structural basis for dual roles of Aar2p in U5 snRNP assembly. Genes and Development, 27(5), 525-540. doi:10.1101/gad.213207.113.

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 Creators:
Weber, G., Author
Cristao, V. F., Author
Santos, K. F., Author
Mozaffari-Jovin, S.1, Author              
Heroven, A. C., Author
Holton, N., Author
Lührmann, R.1, Author              
Beggs, J. D., Author
Wahl, M. C., Author
Affiliations:
1Department of Cellular Biochemistry, MPI for biophysical chemistry, Max Planck Society, ou_578576              

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Free keywords: assembly chaperone; pre-mRNA splicing; regulation by phosphorylation; snRNP biogenesis and recycling; X-ray crystallography
 Abstract: Yeast U5 small nuclear ribonucleoprotein particle (snRNP) is assembled via a cytoplasmic precursor that contains the U5-specific Prp8 protein but lacks the U5-specific Brr2 helicase. Instead, pre-U5 snRNP includes the Aar2 protein not found in mature U5 snRNP or spliceosomes. Aar2p and Brr2p bind competitively to a C-terminal region of Prp8p that comprises consecutive RNase H-like and Jab1/MPN-like domains. To elucidate the molecular basis for this competition, we determined the crystal structure of Aar2p in complex with the Prp8p RNase H and Jab1/MPN domains. Aar2p binds on one side of the RNase H domain and extends its C terminus to the other side, where the Jab1/MPN domain is docked onto a composite Aar2p–RNase H platform. Known Brr2p interaction sites of the Jab1/MPN domain remain available, suggesting that Aar2p-mediated compaction of the Prp8p domains sterically interferes with Brr2p binding. Moreover, Aar2p occupies known RNA-binding sites of the RNase H domain, and Aar2p interferes with binding of U4/U6 di-snRNA to the Prp8p C-terminal region. Structural and functional analyses of phospho-mimetic mutations reveal how phosphorylation reduces affinity of Aar2p for Prp8p and allows Brr2p and U4/U6 binding. Our results show how Aar2p regulates both protein and RNA binding to Prp8p during U5 snRNP assembly.

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Language(s): eng - English
 Dates: 2013-02-262013-03-01
 Publication Status: Published in print
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 Rev. Type: Peer
 Identifiers: DOI: 10.1101/gad.213207.113
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Title: Genes and Development
Source Genre: Journal
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Pages: - Volume / Issue: 27 (5) Sequence Number: - Start / End Page: 525 - 540 Identifier: -