beta-propeller domains as novel RNA-binding modules

所有细胞rna都嵌入到rna -蛋白复合物中，形成动态RNPs，以促进其各种功能。这不仅适用于表征良好的非编码rna，如小核rna的核糖体（snRNPs），也适用于被纳入mRNPs的mrna。在转录过程中，动态的pre-mRNPs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（RNA binding proteins, rbp）是RNA结合蛋白的核心因子。例如，这个庞大而多样的蛋白质家族可以作为支架或促进RNPs的酶活性。rbp直接与RNA接触，因此包含专门的结构域或基序，这些结构域被称为RNA结合域（rbd）。虽然存在成千上万的rbd，但只有相当少的rbd被表征。与DNA结合域不同，DNA结合域通常与双链DNA的主要或次要凹槽相互作用，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。我们鉴定并表征了NHL （NCL-1, HT2A, Lin41）结构域为新型RBD。它由所谓的β-螺旋桨褶皱组成，其中几个β片（“叶片”）被组织成一个“螺旋桨”状结构。序列特异性RNA识别是通过RNA碱基与位于β-螺旋桨叶片间隙中的氨基酸残基的明显接触来实现的。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，我们推断其中一些结构域可能也含有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.