SR and SR-related proteins redistribute to segregated fibrillar components of nucleoli in a response to DNA damage
SR and SR-related proteins redistribute to segregated fibrillar components of nucleoli in a response to DNA damage
复制标题
SR 和 SR 相关蛋白在 DNA 损伤响应中重新分布到核仁分离的纤维成分
作者：
E. Sakashita;H. Endo
在生理条件和细胞刺激下，剪接因子常被重新分配到核仁中。在末期细胞核中，富含丝氨酸的精氨酸(SR)蛋白通常存在于核斑点中，短暂地定位于核糖体DNA(RDNA)活性转录位点，称为核仁组织区域相关斑块(NAP)。在这里，我们发现紫外线和DNA损伤化学物质诱导SR和SR相关蛋白重新分布到间期核中核仁纤维成分周围的区域，这些区域类似于NAP，但不同于NAP，这些区域被称为DNA损伤诱导NAP(d-NAP)。新生RNA的体内标记将d-NAPs与NAPs区分开来，因为即使在DNA损伤导致rDNA转录完全停止后，也能观察到d-NAPs。在各种条件下的研究表明，d-NAP的形成既需要依赖于RNA聚合酶II的转录停止，也需要核仁分离，特别是颗粒核仁成分的解体。尽管SR蛋白重新分布，但富含剪接因子的核斑点并未中断，因为其他核斑点成分，如核多聚(A)RNA和U5-116K蛋白，仍留在DNA损伤的细胞中。这些数据表明，剪接因子的选择性重新分布有助于通过RNA代谢调节特定基因。最后，我们证明了凋亡相关基因选择性剪接的变化与d-NAP的发生是相协调的。我们的结果揭示了对DNA损伤的一种新的反应，涉及剪接因子到核仁的动态重新分配。
Pre-mRNA splicing factors are often redistributed to nucleoli in response to physiological conditions and cell stimuli. In telophase nuclei, serine-arginine rich (SR) proteins, which usually reside in nuclear speckles, localize transiently to active ribosomal DNA (rDNA) transcription sites called nucleolar organizing region-associated patches (NAPs). Here, we show that ultraviolet light and DNA damaging chemicals induce the redistribution of SR and SR-related proteins to areas around nucleolar fibrillar components in interphase nuclei that are similar to, but distinct from, NAPs, and these areas have been termed DNA damage-induced NAPs (d-NAPs). In vivo labeling of nascent RNA distinguished d-NAPs from NAPs in that d-NAPs were observed even after full rDNA transcriptional arrest as a result of DNA damage. Studies under a variety of conditions revealed that d-NAP formation requires both RNA polymerase II-dependent transcriptional arrest and nucleolar segregation, in particular, the disorganization of the granular nucleolar components. Despite the redistribution of SR proteins, splicing factor-enriched nuclear speckles were not disrupted because other nuclear speckle components, such as nuclear poly(A) RNA and the U5-116K protein, remained in DNA-damaged cells. These data suggest that the selective redistribution of splicing factors contributes to the regulation of specific genes via RNA metabolism. Finally, we demonstrate that a change in alternative splicing of apoptosis-related genes is coordinated with the occurrence of d-NAPs. Our results reveal a novel response to DNA damage that involves the dynamic redistribution of splicing factors to nucleoli.
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DOI：
10.1016/0167-4781(85)90002-8
发表时间：
1985-12
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
B. Yung;H. Busch;P. Chan
通讯作者：
B. Yung;H. Busch;P. Chan
影响因子：
4.1
作者：
Kennedy, LJ;Moore, K;Dedon, PC
通讯作者：
Dedon, PC
影响因子：
3.7
作者：
Haaf, T;Ward, DC
通讯作者：
Ward, DC
影响因子：
16
作者：
Yik, JHN;Chen, RC;Zhou, Q
通讯作者：
Zhou, Q
影响因子：
16
作者：
Das, Rita;Yu, Jiong;Reed, Robin
通讯作者：
Reed, Robin