Cross regulation of RNA Binding Proteins and Ordered Protein Aggregation

许多RNA结合蛋白含有一个富含甘氨酸的结构域(GRD)。含有GRD的限制性商业惯例受到严格调控，以避免自发自组装/聚集成细胞质内含物和/或其核耗尽。GRD介导的同型(和异型)蛋白质-蛋白质相互作用可能调节RBP的活性、功能特异性和亚细胞定位。HnRNP A1是一种高度丰富的含有GRD的RBP。它以两种主要的剪接形式存在：A1和A1B，后者是由包含替代外显子7B引起的，该外显子有效地将C-末端GRD扩展了56个残基。虽然hnRNP A1是众所周知的结构性和选择性剪接调节因子，但关于这种较长的异构体的信息很少。最近的一篇论文描述了位于hnRNP A1 GRD内的保守残基(D262N)的一个点突变，它可以驱动hnRNP A1聚集。HnRNP A1聚集的功能后果(S)尚不清楚。

Many RNA binding proteins contain a glycine-rich domain (GRD). GRD-containing RBPs are tightly regulated in order to avoid spontaneous self-assembly/aggregation into cytoplasmic inclusions and/or their nuclear depletion. Homotypic (and heterotypic) protein-protein interactions mediated by the GRD may regulate RBP activity, functional specificity, and subcellular localization. hnRNP A1 is a highly abundant GRD-containing RBP. It exists in two main splice forms: A1 and A1B, the latter arising from the inclusion of an alternative exon 7B which effectively expands the C-terminal GRD by 56 residues. While hnRNP A1 is a well-known regulator of constitutive and alternative splicing, little information is available on this longer isoform. A recent paper describes a point mutation of a conserved residue (D262N) located within the GRD of hnRNP A1 that can drive hnRNP A1 aggregation. The functional consequence(s) of hnRNP A1 aggregation is (are) unknown.