The zinc fingers of the SR-like protein ZRANB2 are single-stranded RNA-binding domains that recognize 5' splice site-like sequences.

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  • Additional Information
    • Source:
      Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : National Academy of Sciences
    • Subject Terms:
      RNA Splice Sites* ; Zinc Fingers*; RNA/*metabolism ; RNA-Binding Proteins/*chemistry; Amino Acid Sequence ; Binding Sites ; Humans ; Protein Structure, Tertiary ; RNA-Binding Proteins/metabolism
    • Abstract:
      The alternative splicing of mRNA is a critical process in higher eukaryotes that generates substantial proteomic diversity. Many of the proteins that are essential to this process contain arginine/serine-rich (RS) domains. ZRANB2 is a widely-expressed and highly-conserved RS-domain protein that can regulate alternative splicing but lacks canonical RNA-binding domains. Instead, it contains 2 RanBP2-type zinc finger (ZnF) domains. We demonstrate that these ZnFs recognize ssRNA with high affinity and specificity. Each ZnF binds to a single AGGUAA motif and the 2 domains combine to recognize AGGUAA(N(x))AGGUAA double sites, suggesting that ZRANB2 regulates alternative splicing via a direct interaction with pre-mRNA at sites that resemble the consensus 5' splice site. We show using X-ray crystallography that recognition of an AGGUAA motif by a single ZnF is dominated by side-chain hydrogen bonds to the bases and formation of a guanine-tryptophan-guanine "ladder." A number of other human proteins that function in RNA processing also contain RanBP2 ZnFs in which the RNA-binding residues of ZRANB2 are conserved. The ZnFs of ZRANB2 therefore define another class of RNA-binding domain, advancing our understanding of RNA recognition and emphasizing the versatility of ZnF domains in molecular recognition.
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    • Grant Information:
      Y1-CO-1020 United States CO NCI NIH HHS; Y1-GM-1104 United States GM NIGMS NIH HHS
    • Molecular Sequence:
      PDB 2K1P; 3G9Y
    • Accession Number:
      0 (RNA Splice Sites)
      0 (RNA-Binding Proteins)
      0 (ZRANB2 protein, human)
      63231-63-0 (RNA)
    • Publication Date:
      Date Created: 20090324 Date Completed: 20090506 Latest Revision: 20211020
    • Publication Date:
      20221213
    • Accession Number:
      PMC2667063
    • Accession Number:
      10.1073/pnas.0802466106
    • Accession Number:
      19304800