beta-propeller domains as novel RNA-binding modules

β-螺旋桨结构域作为新型 RNA 结合模块

• 批准号: 313644909
• 负责人: Professor Dr. Gunter Meister
• 金额: --
• 依托单位: Lehrstuhl für Biochemie I
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/313644909?language=en
• 关键词: beta; propeller; domains; novel; RNA

All cellular RNAs are embedded into RNA-protein complexes and form dynamic RNPs to facilitate their various functions. This is not only true for well-characterized non-coding RNPs such as ribosomes of small nuclear RNPs (snRNPs), but also for mRNAs, which are incorporated into mRNPs. Already during transcription, dynamic pre-mRNPs form that are subsequently remodeled until they reach ribosomes for translation. Besides the RNA itself, RNA binding proteins (RBPs) are central factors within RNPs. This large and diverse protein family can, for example, serve as scaffold or contribute enzymatic activity to RNPs. RBPs directly contact the RNA and therefore contain specialized domains or motifs, which are referred to as RNA binding domains (RBDs). Although thousands of RBPs exist, only a rather small number of RBDs have been characterized. Unlike DNA binding domains, which often interact with the major or the minor groove of double stranded DNA, many single stranded RBDs interact with individual bases and thus contact highly specific RNA motifs.We identified and characterized the NHL (NCL-1, HT2A, Lin41) domain as novel RBD. It is composed of a so-called β-propeller fold, in which several β-sheets (‘blades’) are organized in a ‘propeller’-like structure. Sequence-specific RNA recognition is achieved by distinct contacts of RNA bases with amino acid residues located in the clefts between the blades of the β-propeller. WD40 domains are also composed of β-propeller structures. WD40 domains are among the most abundant protein domains and therefore, we reasoned that some of these domains might also contain RNA binding activity. This hypothesis forms the basis of our project proposal and we hope that we can contribute insights into the various ways of protein-RNA interaction.

所有的细胞RNA都嵌入到RNA-蛋白质复合物中，形成动态RNP以促进其各种功能。这不仅适用于充分表征的非编码RNP，如小核RNP的核糖体（snRNP），而且适用于掺入mRNP的mRNA。在转录过程中，已经形成了动态的pre-mRNP，随后被重塑，直到它们到达核糖体进行翻译。除了RNA本身，RNA结合蛋白（RBP）是RNP中的核心因素。例如，这种大而多样的蛋白质家族可以作为RNP的支架或贡献酶活性。RBP直接接触RNA，因此含有专门的结构域或基序，称为RNA结合结构域（RBD）。虽然存在着数以千计的限制性商业惯例，但只有相当少的限制性商业惯例得到了定性。与DNA结合结构域通常与双链DNA的大沟或小沟相互作用不同，许多单链RBD与单个碱基相互作用，从而接触高度特异性的RNA基序。它由所谓的β-螺旋桨折叠组成，其中几个β-片（“叶片”）以“螺旋桨”状结构组织。序列特异性RNA识别是通过RNA碱基与位于β-螺旋桨叶片之间的裂缝中的氨基酸残基的不同接触来实现的。WD 40结构域也由β-螺旋桨结构组成。WD 40结构域是最丰富的蛋白质结构域之一，因此，我们推断这些结构域中的一些也可能含有RNA结合活性。这一假设构成了我们项目提案的基础，我们希望我们可以对蛋白质-RNA相互作用的各种方式做出贡献。