6TR0

Solution structure of U2AF2 RRM1,2

Summary for 6TR0

• Entry DOI: 10.2210/pdb6tr0/pdb
• NMR Information: BMRB: 34466
• Descriptor: Splicing factor U2AF 65 kDa subunit (1 entity in total)
• Functional Keywords: 3'-splice site, polypyrimidine tract, splicing regulation, splicing
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 22342.49

Authors

Kang, H.-S.,Sattler, M. (deposition date: 2019-12-17, release date: 2020-05-06, Last modification date: 2024-06-19)

Primary citation

Kang, H.S.,Sanchez-Rico, C.,Ebersberger, S.,Sutandy, F.X.R.,Busch, A.,Welte, T.,Stehle, R.,Hipp, C.,Schulz, L.,Buchbender, A.,Zarnack, K.,Konig, J.,Sattler, M.
An autoinhibitory intramolecular interaction proof-reads RNA recognition by the essential splicing factor U2AF2.
Proc.Natl.Acad.Sci.USA, 117:7140-7149, 2020

PubMed Abstract: The recognition of -regulatory RNA motifs in human transcripts by RNA binding proteins (RBPs) is essential for gene regulation. The molecular features that determine RBP specificity are often poorly understood. Here, we combined NMR structural biology with high-throughput iCLIP approaches to identify a regulatory mechanism for U2AF2 RNA recognition. We found that the intrinsically disordered linker region connecting the two RNA recognition motif (RRM) domains of U2AF2 mediates autoinhibitory intramolecular interactions to reduce nonproductive binding to weak Py-tract RNAs. This proofreading favors binding of U2AF2 at stronger Py-tracts, as required to define 3' splice sites at early stages of spliceosome assembly. Mutations that impair the linker autoinhibition enhance the affinity for weak Py-tracts result in promiscuous binding of U2AF2 along mRNAs and impact on splicing fidelity. Our findings highlight an important role of intrinsically disordered linkers to modulate RNA interactions of multidomain RBPs.

PubMed: 32188783
DOI: 10.1073/pnas.1913483117

Experimental method

SOLUTION NMR