beta-propeller domains as novel RNA-binding modules

所有的细胞RNA都被嵌入到RNA-蛋白质复合体中，形成动态的RNPs，以促进它们的各种功能。这不仅适用于特征明确的非编码RNPs，如小核RNPs的核糖体(SnRNPs)，而且也适用于并入mRNPs的mRNAs。在转录过程中，动态的前mRNPs已经形成，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(RBPs)也是RNPs的核心因素。例如，这个庞大而多样的蛋白质家族可以作为支架或为RNPs贡献酶活性。限制性商业惯例直接与RNA接触，因此含有专门的结构域或基序，称为RNA结合域(RBD)。尽管存在数以千计的限制性商业惯例，但只有相当少量的限制性商业惯例得到了描述。与通常与双链DNA的主槽或次槽相互作用的DNA结合域不同，许多单链RBD与单个碱基相互作用，从而接触高度特异的RNA基序。我们鉴定并鉴定了NHL(NCL-1，HT2A，Lin41)结构域为新的RBD。它由所谓的β螺旋桨折叠组成，在该折叠中，几个β-Sheet(叶片)被组织成类似螺旋桨的结构。序列特异的RNA识别是通过RNA碱基与位于β-螺旋桨叶片之间裂隙中的氨基酸残基的不同接触来实现的。WD40结构域也由β-螺旋桨结构组成。WD40结构域是最丰富的蛋白质结构域之一，因此，我们推测其中一些结构域可能也包含RNA结合活性。这一假设构成了我们项目提案的基础，我们希望我们可以为蛋白质-RNA相互作用的各种方式提供见解。

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.