...
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The Zinc Fingers Of The Sr-like Protein Zranb2 Are Single-stranded Rna-binding Domains That Recognize 5' Splice Site-like Sequences
【24h】

The Zinc Fingers Of The Sr-like Protein Zranb2 Are Single-stranded Rna-binding Domains That Recognize 5' Splice Site-like Sequences

机译:Sr样蛋白Zranb2的锌指是识别5'剪接位点样序列的单链Rna结合域。

获取原文
获取原文并翻译 | 示例
           

摘要

The alternative splicing of mRNA is a critical process in higher eu-karyotes 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.
机译:mRNA的可变剪接是产生大量蛋白质组学多样性的高等真核生物的关键过程。此过程必不可少的许多蛋白质都包含精氨酸/富含丝氨酸(RS)的结构域。 ZRANB2是一种广泛表达且高度保守的RS结构域蛋白,可调节其他剪接,但缺少规范的RNA结合结构域。而是包含2个RanBP2型锌指(ZnF)域。我们证明这些ZnFs识别具有高亲和力和特异性的ssRNA。每个ZnF都与单个AGGUAA基序结合,并且两个结构域结合在一起以识别AGGUAA(N_x)AGGUAA双位点,这表明ZRANB2通过与pre-mRNA的直接相互作用在类似于共有5'剪接位点的位点来调控选择性剪接。我们使用X射线晶体学显示,单个ZnF对AGGUAA基序的识别主要由与碱基的侧链氢键和鸟嘌呤-色氨酸-鸟嘌呤“阶梯”的形成决定。在RNA加工中起作用的许多其他人类蛋白质也包含RanBP2 ZnF,其中ZRANB2的RNA结合残基是保守的。因此,ZRANB2的ZnF定义了另一类RNA结合结构域,从而增进了我们对RNA识别的理解,并强调了ZnF结构域在分子识别中的多功能性。

著录项

  • 来源
  • 作者单位

    School of Molecular and Microbial Biosciences and School of Medical Sciences, University of Sydney, Sydney NSW 2006, Australia;

    School of Molecular and Microbial Biosciences and School of Medical Sciences, University of Sydney, Sydney NSW 2006, Australia;

    School of Molecular and Microbial Biosciences and School of Medical Sciences, University of Sydney, Sydney NSW 2006, Australia;

    School of Molecular and Microbial Biosciences and School of Medical Sciences, University of Sydney, Sydney NSW 2006, Australia;

    School of Molecular and Microbial Biosciences and School of Medical Sciences, University of Sydney, Sydney NSW 2006, Australia;

    School of Molecular and Microbial Biosciences and School of Medical Sciences, University of Sydney, Sydney NSW 2006, Australia;

    School of Molecular and Microbial Biosciences and School of Medical Sciences, University of Sydney, Sydney NSW 2006, Australia;

    School of Molecular and Microbial Biosciences and School of Medical Sciences, University of Sydney, Sydney NSW 2006, Australia;

    School of Molecular and Microbial Biosciences and School of Medical Sciences, University of Sydney, Sydney NSW 2006, Australia;

    School of Molecular and Microbial Biosciences and School of Medical Sciences, University of Sydney, Sydney NSW 2006, Australia;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    protein structure; ranbp2 zinc fingers; rna-binding proteins; splicing;

    机译:蛋白质结构;ranbp2锌指;rna结合蛋白;剪接;

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号