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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- Fionna E. Loughlin
- School of Molecular and Microbial Biosciences and School of Medical Sciences, University of Sydney, Sydney NSW 2006, Australia
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- Robyn E. Mansfield
- School of Molecular and Microbial Biosciences and School of Medical Sciences, University of Sydney, Sydney NSW 2006, Australia
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- Paula M. Vaz
- School of Molecular and Microbial Biosciences and School of Medical Sciences, University of Sydney, Sydney NSW 2006, Australia
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- Aaron P. McGrath
- School of Molecular and Microbial Biosciences and School of Medical Sciences, University of Sydney, Sydney NSW 2006, Australia
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- Surya Setiyaputra
- School of Molecular and Microbial Biosciences and School of Medical Sciences, University of Sydney, Sydney NSW 2006, Australia
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- Roland Gamsjaeger
- School of Molecular and Microbial Biosciences and School of Medical Sciences, University of Sydney, Sydney NSW 2006, Australia
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- Eva S. Chen
- School of Molecular and Microbial Biosciences and School of Medical Sciences, University of Sydney, Sydney NSW 2006, Australia
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- Brian J. Morris
- School of Molecular and Microbial Biosciences and School of Medical Sciences, University of Sydney, Sydney NSW 2006, Australia
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- J. Mitchell Guss
- School of Molecular and Microbial Biosciences and School of Medical Sciences, University of Sydney, Sydney NSW 2006, Australia
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- Joel P. Mackay
- School of Molecular and Microbial Biosciences and School of Medical Sciences, University of Sydney, Sydney NSW 2006, Australia
Abstract
<jats:p> 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 <jats:sub>x</jats:sub> )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. </jats:p>
Journal
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 106 (14), 5581-5586, 2009-04-07
Proceedings of the National Academy of Sciences
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Details 詳細情報について
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- CRID
- 1360574094842263424
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- ISSN
- 10916490
- 00278424
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- Data Source
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- Crossref