Cross regulation of RNA Binding Proteins and Ordered Protein Aggregation

RNA 结合蛋白和有序蛋白聚集的交叉调控

• 批准号: RGPIN-2015-06030
• 负责人: VandeVelde, Christine
• 金额: $ 2.48万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629187
• 关键词: Cross; regulation; RNA; Binding; Proteins

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.

许多RNA结合蛋白含有富含甘氨酸的结构域（GRD）。含有GRD的RBP受到严格调控，以避免自发自组装/聚集成细胞质内含物和/或其核耗竭。GRD介导的同型（和异型）蛋白质-蛋白质相互作用可调节RBP活性、功能特异性和亚细胞定位。hnRNP A1是一种高丰度的含GRD的RBP。它以两种主要剪接形式存在：A1和A1 B，后者是由于包含了一个选择性外显子7 B，有效地将C-末端GRD扩展了56个残基。虽然hnRNP A1是一个众所周知的组成性和选择性剪接的调节器，但关于这种较长的同种型的信息很少。最近的一篇论文描述了位于hnRNP A1的GRD内的保守残基（D262 N）的点突变，该点突变可以驱动hnRNP A1聚集。hnRNP A1聚集的功能后果尚不清楚。