Hall Lisa L, Smith Kelly P, Byron Meg, Lawrence Jeanne B
Department of Cell Biology, University of Massachusetts Medical School, Worcester, 01655, USA.
Anat Rec A Discov Mol Cell Evol Biol. 2006 Jul;288(7):664-75. doi: 10.1002/ar.a.20336.
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 component. 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.
特定基因、RNA和蛋白质的直接定位，使得人们能够剖析单个核斑与基因表达分子生物学之间的关系。核斑（又称SC35结构域）本质上是普遍存在的结构，富含大多数前体mRNA代谢因子，但其与基因表达的关系一直未被充分理解。对特定基因及其剪接或成熟mRNA的分析有力地支持了SC35结构域是活性中心，而非与基因表达分离的惰性因子储存库。我们提出，SC35结构域是将特定前体mRNA的表达与大量RNA代谢复合物的快速循环在空间上联系起来的中心，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外，基因表达的连续步骤在每个SC35结构域在结构上是整合的，这与转录、剪接和mRNA输出的生化机制相互偶联的其他证据一致。转录和剪接在周边区域进行亚区室化，大部分剪接后的mRNA在输出之前进入该结构域。此外，本文提出的新发现开始通过定义促进SC35结构域相对于其他成分的解体或组装的磷酸化的特定扰动，来阐明核斑的结构基础。迄今为止的结果与SC35剪接体组装因子作为一个完整的结构成分一致。使SC35分散的条件也会使聚腺苷酸RNA分散，而剪接因子ASF/SF2可以在SC35或SRm300作为核心结构域的完整成分保留的条件下分散。
