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MENε/β noncoding RNAs are essential for structural integrity of nuclear paraspeckles

机译:MENε/β非编码RNA对核副斑点的结构完整性至关重要

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摘要

Recent transcriptome analyses have shown that thousands of non-coding RNAs (ncRNAs) are transcribed from mammalian genomes. Although the number of functionally annotated ncRNAs is still limited, they are known to be frequently retained in the nucleus, where they coordinate regulatory networks of gene expression. Some sub-nuclear organelles or nuclear bodies include RNA species whose identity and structural roles are largely unknown. We identified 2 abundant overlapping ncRNAs, MENe and MEN/J (MENε/β), which are transcribed from the corresponding site in the multiple endocrine neoplasia (MEN) I locus and which localize to nuclear paraspeckles. This finding raises the intriguing possibility that MENε/β are involved in paraspeckle organization, because paraspeckles are, reportedly, Rnase-sensitive structures. Successful removal of MENε/β by a refined knockdown method resulted in paraspeckle disintegration. Furthermore, the reassembly of paraspeckles disassembled by tran-scriptional arrest appeared to be unsuccessful in the absence of MENε/β. RNA interference and immunoprecipitation further revealed that the paraspeckle proteins p54rb and PSF selectively associate with and stabilize the longer MEN/β, thereby contributing to the organization of the paraspeckle structure. The paraspeckle protein PSP1 is not directly involved in either MENε/β stabilization or paraspeckle organization. We postulate a model for nuclear paraspeckle body organization where specific ncRNAs and RNA-binding proteins cooperate to maintain and, presumably, establish the structure.
机译:最近的转录组分析表明,从哺乳动物基因组转录了成千上万个非编码RNA(ncRNA)。尽管功能注释的ncRNA的数量仍然有限,但已知它们经常保留在核中,在核中它们协调基因表达的调控网络。一些亚核细胞器或核小体包括其种类和结构作用很大程度上未知的RNA。我们确定了2个大量重叠的ncRNA,即MENe和MEN / J(MENε/β),它们从多发性内分泌肿瘤(MEN)I基因座的相应位点转录而成,并定位于核旁斑。这一发现提高了MENε/β参与散斑组织的可能性,因为据报道散斑是Rnase敏感结构。通过精制的敲除方法成功去除MENε/β会导致散斑分解。此外,在缺少MENε/β的情况下,通过转录停滞而解体的散斑的重组看来是不成功的。 RNA干扰和免疫沉淀进一步表明,副斑点蛋白p54 / nrb和PSF与较长的MEN /β选择性缔合并稳定它们,从而有助于副斑点结构的组织。副斑点蛋白PSP1不直接参与MENε/β稳定或副斑点组织。我们假设一个核旁散斑身体组织模型,其中特定的ncRNA和RNA结合蛋白可以协同维持并推测其结构。

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  • 作者单位

    Functional Rnomics Team, Biomedicinal Information Research Center, 2-42 Aomi, Koutou, Tokyo 135-0064, Japan;

    Functional Rnomics Team, Biomedicinal Information Research Center, 2-42 Aomi, Koutou, Tokyo 135-0064, Japan Japan Biological Informatics Consortiuni, National Institute of Advanced Industrial Science and Technology, 2-42 Aomi, Koutou, Tokyo 135-0064, Japan;

    Functional Rnomics Team, Biomedicinal Information Research Center, 2-42 Aomi, Koutou, Tokyo 135-0064, Japan Japan Biological Informatics Consortiuni, National Institute of Advanced Industrial Science and Technology, 2-42 Aomi, Koutou, Tokyo 135-0064, Japan;

    RNA Informatics Team, Computational Biology Research Center, 2-42 Aomi, Koutou, Tokyo 135-0064, Japan;

    Functional Rnomics Team, Biomedicinal Information Research Center, 2-42 Aomi, Koutou, Tokyo 135-0064, Japan;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    nuclear bodies; RNA-binding proteins;

    机译:核机构;RNA结合蛋白;

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