Molecular anatomy of a speckle
Molecular anatomy of a speckle
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DOI：
10.1002/ar.a.20336
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发表时间：
2006-07-01
期刊：
影响因子：
--
通讯作者：
Lawrence, Jeanne B.
中科院分区：
文献类型：
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作者：
Hall, Lisa L.;Smith, Kelly P.;Lawrence, Jeanne B.
特定基因、RNA 和蛋白质的直接定位使得能够解剖与基因表达的分子生物学相关的个体核斑点。核斑点（又名 SC35 结构域）本质上是富含大多数前 mRNA 代谢因子的普遍存在的结构，但它们与基因表达的关系却知之甚少。对特定基因及其剪接或成熟 mRNA 的分析强烈支持 SC35 结构域是活性中心，而不是与基因表达分离的惰性因子的储存库。我们认为 SC35 结构域是在空间上将特定前 mRNA 的表达与丰富的 RNA 代谢复合物的快速回收联系起来的枢纽，从而促进许多高活性基因的表达。除了提高每个步骤的效率之外，基因表达的连续步骤在每个 SC35 结构域上进行结构整合，这与转录、剪接和 mRNA 输出的生化机制耦合的其他证据一致。转录和剪接在外围进行亚区室化，大部分剪接的 mRNA 在输出之前进入该结构域。此外，这里提出的新发现通过定义促进 SC35 结构域相对于其他组件的拆卸或组装的特定磷酸化扰动，开始阐明斑点的结构基础。迄今为止的结果与 SC35 剪接体组装因子作为整体结构成分一致。分散 SC35 的条件也会分散聚 (A) RNA，而剪接因子 ASF/SF2 可以在 SC35 或 SRm300 保留为核心结构域的完整组件的条件下分散。
Direct localization of specific genes, RNAs, and proteins has allowed the dissection of individual nuclear speckles in relation to the molecular biology of gene expression. Nuclear speckles (aka SC35 domains) are essentially ubiquitous structures enriched for most pre-mRNA metabolic factors, yet their relationship to gene expression has been poorly understood. Analyses of specific genes and their spliced or mature mRNA strongly support that SC35 domains are hubs of activity, not stores of inert factors detached from gene expression. We propose that SC35 domains are hubs that spatially link expression of specific pre-mRNAs to rapid recycling of copious RNA metabolic complexes, thereby facilitating expression of many highly active genes. In addition to increasing the efficiency of each step, sequential steps in gene expression are structurally integrated at each SC35 domain, consistent with other evidence that the biochemical machineries for transcription, splicing, and mRNA export are coupled. Transcription and splicing are subcompartmentalized at the periphery, with largely spliced mRNA entering the domain prior to export. In addition, new findings presented here begin to illuminate the structural underpinnings of a speckle by defining specific perturbations of phosphorylation that promote disassembly or assembly of an SC35 domain in relation to other components. Results thus far are consistent with the SC35 spliceosome assembly factor as an integral structural compqnent. Conditions that disperse SC35 also disperse poly(A) RNA, whereas the splicing factor ASF/SF2 can be dispersed under conditions in which SC35 or SRm300 remain as intact components of a core domain.