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Title

Structural basis for recognition of the intron branch site RNA by splicing factor 1

Authors
Liu, Z
Luyten, I
Bottomley, M J
Messias, A C
Sprangers, R
Zanier, K
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Published in Science. 2001, vol. 294, no. 5544, p. 1098-102
Abstract During spliceosome assembly, splicing factor 1 (SF1) specifically recognizes the intron branch point sequence (BPS) UACUAAC in the pre-mRNA transcripts. We show that the KH-QUA2 region of SF1 defines an enlarged KH (hn RNP K) fold which is necessary and sufficient for BPS binding. The 3' part of the BPS (UAAC), including the conserved branch point adenosine (underlined), is specifically recognized in a hydrophobic cleft formed by the Gly-Pro-Arg-Gly motif and the variable loop of the KH domain. The QUA2 region recognizes the 5' nucleotides of the BPS (ACU). The branch point adenosine acting as the nucleophile in the first biochemical step of splicing is deeply buried. BPS RNA recognition suggests how SF1 may facilitate subsequent formation of the prespliceosomal complex A.
Keywords Adenosine/chemistry/metabolismAmino Acid MotifsAmino Acid SequenceBinding SitesDNA-Binding ProteinsHumansHydrogen BondingHydrophobic and Hydrophilic InteractionsIntronsModels, MolecularMolecular Sequence DataMutationNuclear Magnetic Resonance, BiomolecularNucleic Acid ConformationProtein ConformationProtein FoldingProtein Structure, SecondaryProtein Structure, TertiaryRNA Precursors/chemistry/metabolismRNA, Messenger/chemistry/metabolismRNA-Binding Proteins/chemistry/genetics/metabolismRecombinant Proteins/chemistry/metabolismSpliceosomes/metabolismTranscription FactorsUracil/chemistry/metabolism
Identifiers
PMID: 11691992
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LIU, Z et al. Structural basis for recognition of the intron branch site RNA by splicing factor 1. In: Science, 2001, vol. 294, n° 5544, p. 1098-102. https://archive-ouverte.unige.ch/unige:17545

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Deposited on : 2011-11-25

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