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An extended U2AF65–RNA-binding domain recognizes the 3′ splice site signal

Author

Listed:
  • Anant A. Agrawal

    (University of Rochester School of Medicine and Dentistry
    Present address: H3 Biomedicine, Boston, Massachusetts 02139, USA.)

  • Enea Salsi

    (University of Rochester School of Medicine and Dentistry)

  • Rakesh Chatrikhi

    (University of Rochester School of Medicine and Dentistry)

  • Steven Henderson

    (University of Rochester School of Medicine and Dentistry)

  • Jermaine L. Jenkins

    (University of Rochester School of Medicine and Dentistry)

  • Michael R. Green

    (Howard Hughes Medical Institute and Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School)

  • Dmitri N. Ermolenko

    (University of Rochester School of Medicine and Dentistry)

  • Clara L. Kielkopf

    (University of Rochester School of Medicine and Dentistry)

Abstract

How the essential pre-mRNA splicing factor U2AF65 recognizes the polypyrimidine (Py) signals of the major class of 3′ splice sites in human gene transcripts remains incompletely understood. We determined four structures of an extended U2AF65–RNA-binding domain bound to Py-tract oligonucleotides at resolutions between 2.0 and 1.5 Å. These structures together with RNA binding and splicing assays reveal unforeseen roles for U2AF65 inter-domain residues in recognizing a contiguous, nine-nucleotide Py tract. The U2AF65 linker residues between the dual RNA recognition motifs (RRMs) recognize the central nucleotide, whereas the N- and C-terminal RRM extensions recognize the 3′ terminus and third nucleotide. Single-molecule FRET experiments suggest that conformational selection and induced fit of the U2AF65 RRMs are complementary mechanisms for Py-tract association. Altogether, these results advance the mechanistic understanding of molecular recognition for a major class of splice site signals.

Suggested Citation

  • Anant A. Agrawal & Enea Salsi & Rakesh Chatrikhi & Steven Henderson & Jermaine L. Jenkins & Michael R. Green & Dmitri N. Ermolenko & Clara L. Kielkopf, 2016. "An extended U2AF65–RNA-binding domain recognizes the 3′ splice site signal," Nature Communications, Nature, vol. 7(1), pages 1-14, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10950
    DOI: 10.1038/ncomms10950
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    Cited by:

    1. Santiago Martínez-Lumbreras & Lena K. Träger & Miriam M. Mulorz & Marco Payr & Varvara Dikaya & Clara Hipp & Julian König & Michael Sattler, 2024. "Intramolecular autoinhibition regulates the selectivity of PRPF40A tandem WW domains for proline-rich motifs," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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