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首页> 外文期刊>Journal of Cell Science >Long nuclear-retained non-coding RNAs and allele-specific higher-order chromatin organization at imprinted snoRNA gene arrays.
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Long nuclear-retained non-coding RNAs and allele-specific higher-order chromatin organization at imprinted snoRNA gene arrays.

机译:在印记的snoRNA基因阵列上保留了长核保留的非编码RNA和等位基因特异性的高级染色质组织。

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摘要

The imprinted Snurf-Snrpn domain, also referred to as the Prader-Willi syndrome region, contains two approximately 100-200 kb arrays of repeated small nucleolar (sno)RNAs processed from introns of long, paternally expressed non-protein-coding RNAs whose biogenesis and functions are poorly understood. We provide evidence that C/D snoRNAs do not derive from a single transcript as previously envisaged, but rather from (at least) two independent transcription units. We show that spliced snoRNA host-gene transcripts accumulate near their transcription sites as structurally constrained RNA species that are prevented from diffusing, as well as multiple stable nucleoplasmic RNA foci dispersed in the entire nucleus but not in the nucleolus. Chromatin structure at these repeated arrays displays an outstanding parent-of-origin-specific higher-order organization: the transcriptionally active allele is revealed as extended DNA FISH signals whereas the genetically identical, silent allele is visualized as singlet DNA FISH signals. A similar allele-specific chromatin organization is documented for snoRNA gene arrays at the imprinted Dlk1-Dio3 domain. Our findings have repercussions for understanding the spatial organization of gene expression and the intra-nuclear fate of non-coding RNAs in the context of nuclear architecture.
机译:印记的Snurf-Snrpn结构域,也称为Prader-Willi综合征区域,包含两个大约100-200 kb的重复小核仁(sno)RNA阵列,这些小核仁(sno)RNA由父本表达长的非蛋白质编码RNA的内含子加工而成和功能了解甚少。我们提供的证据表明,C / D snoRNA并非源自先前设想的单个转录本,而是源自(至少)两个独立的转录单位。我们显示,剪接的snoRNA宿主基因转录物在其转录位点附近积累,作为结构受约束的RNA种类,阻止了扩散,以及分散在整个细胞核中但不在核仁中的多个稳定核质RNA焦点。在这些重复阵列上的染色质结构显示出杰出的起源母体特异性高阶组织:转录活性等位基因显示为扩展的DNA FISH信号,而遗传上相同的沉默等位基因则显示为单峰DNA FISH信号。印记的Dlk1-Dio3域上的snoRNA基因阵列记录了类似的等位基因特异性染色质组织。我们的发现对理解基因表达的空间组织和核结构背景下非编码RNA的核内命运产生了影响。

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