Nonrandom gene organization: structural arrangements of specific pre-mRNA transcription and splicing with SC-35 domains.
Nonrandom gene organization: structural arrangements of specific pre-mRNA transcription and splicing with SC-35 domains.
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DOI：
10.1083/jcb.131.6.1635
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发表时间：
1995-12
期刊：
影响因子：
--
通讯作者：
Lawrence J
中科院分区：
文献类型：
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作者：
Xing Y;Johnson CV;Moen PT Jr;McNeil JA;Lawrence J
这项工作证明了与剪接因子和多聚(a)+ RNA富集的核结构域相关的特定基因的高度非随机分布，并为这些基因直接参与mrna前代谢提供了证据。在数百个二倍体成纤维细胞中研究发现，人胶原I α 1和β -肌动蛋白DNA/RNA与SC-35结构域具有高度的空间关联，而三个非转录基因，肌球蛋白重链、神经紧张素和白蛋白，则没有这种优先关联。胶原I α 1 RNA聚集在结构域的中心区域，而β -肌动蛋白RNA则集中在外围。一种新的方法揭示了胶原蛋白RNA轨道是极化的，整个基因在一端，在结构域的边缘，RNA延伸到结构域。内含子26在结构域外围的RNA轨道内剪接。转录抑制研究表明，结构域的结构及其与基因的关系并不依赖于胶原RNA的持续积累，抑制后剩余的结构域不仅仅是储存位点。结果支持一个模型，该模型调和了光镜和电镜观察结果，该模型提出一些特定基因的转录发生在结构域的边界，这也可能在RNA代谢成分的组装或分布中起作用。与总体未定义hnRNA合成通过结构域间空间的明显随机分散相反，一些基因的转录和剪接优先发生在特定位点，并且高度的个体pre-mRNA代谢被离散的SC-35结构域划分。
This work demonstrates a highly nonrandom distribution of specific genes relative to nuclear domains enriched in splicing factors and poly(A)+ RNA, and provides evidence for the direct involvement of these in pre-mRNA metabolism. As investigated in hundreds of diploid fibroblasts, human collagen I alpha 1 and beta-actin DNA/RNA showed a very high degree of spatial association with SC-35 domains, whereas three nontranscribed genes, myosin heavy chain, neurotensin, and albumin, showed no such preferential association. Collagen I alpha 1 RNA accumulates within the more central region of the domain, whereas beta-actin RNA localizes at the periphery. A novel approach revealed that collagen RNA tracks are polarized, with the entire gene at one end, on the edge of the domain, and the RNA extending into the domain. Intron 26 is spliced within the RNA track at the domain periphery. Transcriptional inhibition studies show both the structure of the domain and the gene's relationship to it are not dependent upon the continued presence of accumulated collagen RNA, and that domains remaining after inhibition are not just storage sites. Results support a model reconciling light and electron microscopic observations which proposes that transcription of some specific genes occurs at the border of domains, which may also function in the assembly or distribution of RNA metabolic components. In contrast to the apparently random dispersal of total undefined hnRNA synthesis through interdomain space, transcription and splicing for some genes occurs preferentially at specific sites, and a high degree of individual pre-mRNA metabolism is compartmentalized with discrete SC-35 domains.