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Initiation of translation in bacteria by a structured eukaryotic IRES RNA

机译：通过结构化真核IRES RNA在细菌中开始翻译

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摘要

翻译对所有活生物的基因表达来说都至关重要，但用来招募核糖体和启动蛋白合成的信号在不同生命领域却截然不同。虽然真核生物和原核生物都通过一个高度保守的核心核糖体结构来翻译mRNA,但mRNA内被核糖体识别的两种信号是却相互排斥的。Jeffrey Kieft及同事想知道是否会有一种被真核生物和原核生物都能识别的普遍信号，他们现在介绍了具有这种性质的一个真核病毒IRES(内部核糖体进入点)元素。该IRES与细菌和真核生物核糖体都能够相似地、以依赖于结构的方式结合，但在细菌中该元素的结合会诱导核糖体位置发生一个变化，这种变化在真核生物核糖体中没有被看到。%The central dogma of gene expression (DNA to RNA to protein) is universal, but in different domains of life there are fundamental mechanistic differences within this pathway. For example, the canonical molecular signals used to initiate protein synthesis in bacteria and eukaryotes are mutually exclusive. However, the core structures and conformational dynamics of ribosomes that are responsible for the translation steps that take place after initiation are ancient and conserved across the domains of life. We wanted to explore whether an undiscovered RNA-based signal might be able to use these conserved features, bypassing mechanisms specific to each domain of life, and initiate protein synthesis in both bacteria and eukaryotes. Although structured internal ribosome entry site (IRES) RNAs can manipulate ribosomes to initiate translation in eukaryotic cells, an analogous RNA structure-based mechanism has not been observed in bacteria. Here we report our discovery that a eukaryotic viral IRES can initiate translation in live bacteria. We solved the crystal structure of this IRES bound to a bacterial ribosome to 3.8 A resolution, revealing that despite differences between bacterial and eukaryotic ribosomes this IRES binds directly to both and occupies the space normally used by transfer RNAs. Initiation in both bacteria and eukaryotes depends on the structure of the IRES RNA, but in bacteria this RNA uses a different mechanism that includes a form of ribosome repositioning after initial recruitment. This IRES RNA bridges billions of years of evolutionary divergence and provides an example of an RNA structure-based translation initiation signal capable of operating in two domains of life.
机译：翻译对所有活生物的基因表达来说都至关重要，但用来招募核糖体和启动蛋白合成的信号在不同生命领域却截然不同。虽然真核生物和原核生物都通过一个高度保守的核心核糖体结构来翻译mRNA,但mRNA内被核糖体识别的两种信号是却相互排斥的。Jeffrey Kieft及同事想知道是否会有一种被真核生物和原核生物都能识别的普遍信号，他们现在介绍了具有这种性质的一个真核病毒IRES(内部核糖体进入点)元素。该IRES与细菌和真核生物核糖体都能够相似地、以依赖于结构的方式结合，但在细菌中该元素的结合会诱导核糖体位置发生一个变化，这种变化在真核生物核糖体中没有被看到。%The central dogma of gene expression (DNA to RNA to protein) is universal, but in different domains of life there are fundamental mechanistic differences within this pathway. For example, the canonical molecular signals used to initiate protein synthesis in bacteria and eukaryotes are mutually exclusive. However, the core structures and conformational dynamics of ribosomes that are responsible for the translation steps that take place after initiation are ancient and conserved across the domains of life. We wanted to explore whether an undiscovered RNA-based signal might be able to use these conserved features, bypassing mechanisms specific to each domain of life, and initiate protein synthesis in both bacteria and eukaryotes. Although structured internal ribosome entry site (IRES) RNAs can manipulate ribosomes to initiate translation in eukaryotic cells, an analogous RNA structure-based mechanism has not been observed in bacteria. Here we report our discovery that a eukaryotic viral IRES can initiate translation in live bacteria. We solved the crystal structure of this IRES bound to a bacterial ribosome to 3.8 A resolution, revealing that despite differences between bacterial and eukaryotic ribosomes this IRES binds directly to both and occupies the space normally used by transfer RNAs. Initiation in both bacteria and eukaryotes depends on the structure of the IRES RNA, but in bacteria this RNA uses a different mechanism that includes a form of ribosome repositioning after initial recruitment. This IRES RNA bridges billions of years of evolutionary divergence and provides an example of an RNA structure-based translation initiation signal capable of operating in two domains of life.

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  • 来源
    《Nature》 |2015年第7541期|110-113A2|共5页
  • 作者

    Timothy M. Colussi; David A. Costantino; Jianyu Zhu; John Paul Donohue; Andrei A. Korostelev; Zane A. Jaafar; Terra-Dawn M. Plank; Harry F. Noller; Jeffrey S. Kieft;

  • 作者单位

    Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA,Howard Hughes Medical Institute, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA,Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, USA;

    Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA,Howard Hughes Medical Institute, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA;

    Center for Molecular Biology of RNA and Department of Molecular, Cell and Developmental Biology, Sinsheimer Labs, University of California at Santa Cruz, Santa Cruz, California 95064, USA,Cocrystal Discovery. Inc., Mountain View, California 94043, USA;

    Center for Molecular Biology of RNA and Department of Molecular, Cell and Developmental Biology, Sinsheimer Labs, University of California at Santa Cruz, Santa Cruz, California 95064, USA;

    Center for Molecular Biology of RNA and Department of Molecular, Cell and Developmental Biology, Sinsheimer Labs, University of California at Santa Cruz, Santa Cruz, California 95064, USA,RNA Therapeutics Institute, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA;

    Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA;

    Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA,Department of Reproductive Medicine, University of California at San Diego, La Jolla California 92093, USA;

    Center for Molecular Biology of RNA and Department of Molecular, Cell and Developmental Biology, Sinsheimer Labs, University of California at Santa Cruz, Santa Cruz, California 95064, USA;

    Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA,Howard Hughes Medical Institute, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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