S1-1 nuclear domains: characterization and dynamics as a function of transcriptional activity
S1-1 nuclear domains: characterization and dynamics as a function of transcriptional activity
复制标题
DOI：
10.1042/bc20070142
复制
发表时间：
2008-09-01
影响因子：
2.7
通讯作者：
Tani, Tokio
中科院分区：
文献类型：
--
作者：
Inoue, Akira;Tsugawa, Katsuji;Tani, Tokio
背景资料。RNA结合蛋白S1-1，也称为RBM 10（RNA结合基序10），是推定的肿瘤抑制因子RBM 5的一部分，并且与癌症增殖和凋亡相关。在本研究中，我们研究了S1- 1的细胞生物学。S1-1存在于核仁核质的数百个点状和不规则区域中。其中约1040个结构域大于0.5 μ m，对于S1-1免疫染色很突出。这些结构域（S1-1核小体）通常存在于组织细胞和培养细胞中。当细胞转录被热休克，血清饥饿，培养在高细胞密度或抑制RNA聚合酶II抑制剂，小S1-1域（S1-1颗粒），与弱的免疫染色信号，在数量上减少，而S1-1核小体变得突出，并增加了大小。当细胞置于正常条件下时，这些改变的S1-1结构域恢复到初始状态。与旁斑相似，S1-1核小体与核斑或IGC（染色质间颗粒簇）紧密相邻，如免疫电镜所示。然而，S1-1核体并不对应于旁斑或IGAZ（染色质颗粒间相关区），而是与TIDRs（转录失活依赖性RNA结构域）相一致，我们以前在RNA水平上对其进行了表征。扩大的S1-1核体/TIDRs积累了S1-1蛋白，并显微注射了初级和剪接的mRNA，推测是为了以后的基因表达升高。此外，电子显微镜显示S1-1也存在于染色质纤维周围，这表明在更高分辨率下观察到S1-1颗粒的结构。S1-1由数百个核结构域组成，这些核结构域以可逆的方式动态地改变它们的结构。在RNA聚合酶II转录全面减少后，S1-1核小体的数量增加和减少。它们是不同于旁斑或IGAZ的新结构域，尽管它们类似地发生在核斑附近。我们讨论S1-1颗粒与基因表达的关系。此外，这是第一个TIDR定位蛋白的报告。
Background information. The RNA-binding protein S1-1, also called RBM10 (RNA-binding motif 10), is a paralogue of putative tumour suppressor RBM5 and has been correlated with cancer proliferation and apoptosis. In the present study, we have investigated the cell biology of S1-1.Results. In the extranucleolar nucleoplasm, S1-1 occurred in hundreds of punctate and irregular domains. Some 1040 of these domains were larger than 0.5 mu m and prominent for S1-1 immunostaining. These domains (S1-1 nuclear bodies) were commonly present in tissue cells and in cultured cells. When cellular transcription was globally reduced by heat shock, serum starvation, culture at high cell densities or inhibition with RNA polymerase II inhibitors, small S1-1 domains (S1-1 granules), with weak immunostaining signals, reduced in number, whereas S1-1 nuclear bodies became prominent and increased in size. These altered S1-1 domains were returned to initial states when the cells were placed under normal conditions. Similar to paraspeckles, S1-1 nuclear bodies occurred closely adjacent to nuclear speckles or IGCs (interchromatin granule clusters), as determined by immunoelectron microscopy. However, the S1-1 nuclear bodies did not correspond to paraspeckles or IGAZs (interchromatin-granule-associated zones), but coincided with TIDRs (transcription-inactivation-dependent RNA domains), which we had characterized previously at the RNA level. The enlarged S1-1 nuclear bodies/TIDRs accumulated the S1-1 protein and microinjected primary and spliced mRNAs, presumably for later elevation of gene expression. In addition, electron microscopy revealed that S1-1 was also present on perichromatin fibrils, suggesting the structure of S1-1 granules seen at higher resolution.Conclusions. S1-1 constitutes hundreds of nuclear domains, which dynamically change their structures in a reversible manner. Upon globally reducing RNA polymerase II transcription, S1-1 nuclear bodies enlarge and decrease in number. They are novel domains different from paraspeckles or IGAZs, despite their similar occurrence adjacent to nuclear speckles. We discuss S1-1 granules in terms of their association with gene expression. In addition, this is the first report of a TIDR-localized protein.