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Elucidation of the aberrant 3′ splice site selection by cancer-associated mutations on the U2AF1

Author

Listed:
  • Hisashi Yoshida

    (Yokohama City University)

  • Sam-Yong Park

    (Yokohama City University)

  • Gyosuke Sakashita

    (Shimane University School of Medicine)

  • Yuko Nariai

    (Shimane University School of Medicine)

  • Kanako Kuwasako

    (Musashino University)

  • Yutaka Muto

    (Musashino University)

  • Takeshi Urano

    (Shimane University School of Medicine)

  • Eiji Obayashi

    (Shimane University School of Medicine)

Abstract

The accurate exclusion of introns by RNA splicing is critical for the production of mature mRNA. U2AF1 binds specifically to the 3´ splice site, which includes an essential AG dinucleotide. Even a single amino acid mutation of U2AF1 can cause serious disease such as certain cancers or myelodysplastic syndromes. Here, we describe the first crystal structures of wild-type and pathogenic mutant U2AF1 complexed with target RNA, revealing the mechanism of 3´ splice site selection, and how aberrant splicing results from clinically important mutations. Unexpected features of this mechanism may assist the future development of new treatments against diseases caused by splicing errors.

Suggested Citation

  • Hisashi Yoshida & Sam-Yong Park & Gyosuke Sakashita & Yuko Nariai & Kanako Kuwasako & Yutaka Muto & Takeshi Urano & Eiji Obayashi, 2020. "Elucidation of the aberrant 3′ splice site selection by cancer-associated mutations on the U2AF1," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18559-6
    DOI: 10.1038/s41467-020-18559-6
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    Cited by:

    1. Keyun Wang & Li Zhang & Sirui Zhang & Ye Liu & Jiawei Mao & Zhen Liu & Lin Xu & Kejia Li & Jianshu Wang & Yanni Ma & Jiayi Wang & Haitao Li & Zefeng Wang & Guohui Li & Hong Cheng & Mingliang Ye, 2024. "Metabolic labeling based methylome profiling enables functional dissection of histidine methylation in C3H1 zinc fingers," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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