Galganski Lukasz, Urbanek Martyna O, Krzyzosiak Wlodzimierz J
Department of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.
Nucleic Acids Res. 2017 Oct 13;45(18):10350-10368. doi: 10.1093/nar/gkx759.
The nucleoplasm is not homogenous; it consists of many types of nuclear bodies, also known as nuclear domains or nuclear subcompartments. These self-organizing structures gather machinery involved in various nuclear activities. Nuclear speckles (NSs) or splicing speckles, also called interchromatin granule clusters, were discovered as sites for splicing factor storage and modification. Further studies on transcription and mRNA maturation and export revealed a more general role for splicing speckles in RNA metabolism. Here, we discuss the functional implications of the localization of numerous proteins crucial for epigenetic regulation, chromatin organization, DNA repair and RNA modification to nuclear speckles. We highlight recent advances suggesting that NSs facilitate integrated regulation of gene expression. In addition, we consider the influence of abundant regulatory and signaling proteins, i.e. protein kinases and proteins involved in protein ubiquitination, phosphoinositide signaling and nucleoskeletal organization, on pre-mRNA synthesis and maturation. While many of these regulatory proteins act within NSs, direct evidence for mRNA metabolism events occurring in NSs is still lacking. NSs contribute to numerous human diseases, including cancers and viral infections. In addition, recent data have demonstrated close relationships between these structures and the development of neurological disorders.
核质并非均匀一致；它由多种类型的核体组成，也被称为核结构域或核亚区室。这些自组织结构聚集了参与各种核活动的机制。核斑点（NSs）或剪接斑点，也称为染色质间颗粒簇，最初被发现是剪接因子储存和修饰的位点。对转录、mRNA成熟和输出的进一步研究揭示了剪接斑点在RNA代谢中更广泛的作用。在这里，我们讨论了众多对表观遗传调控、染色质组织、DNA修复和RNA修饰至关重要的蛋白质定位于核斑点的功能意义。我们强调了最近的进展，这些进展表明核斑点促进了基因表达的整合调控。此外，我们考虑了丰富的调节和信号蛋白，即蛋白激酶以及参与蛋白质泛素化、磷酸肌醇信号传导和核骨架组织的蛋白质，对前体mRNA合成和成熟的影响。虽然这些调节蛋白中的许多在核斑点内起作用，但仍缺乏在核斑点中发生mRNA代谢事件的直接证据。核斑点与多种人类疾病有关，包括癌症和病毒感染。此外，最近的数据表明这些结构与神经疾病的发展密切相关。
