BACKGROUND Many long noncoding RNAs (lncRNAs) have been implicated in general and cell type-specific molecular regulation. Here, we asked what underlies the fundamental basis for the seemingly random appearance of nuclear lncRNA condensates in cells, and we sought compounds that can promote the disintegration of lncRNA condensates in vivo. RESULTS As a basis for comparing lncRNAs and cellular properties among different cell types, we screened lncRNAs in human pluripotent stem cells (hPSCs) that were differentiated to an atlas of cell lineages. We found that paraspeckles, which form by aggregation of the lncRNA NEAT1, are scaled by the size of the nucleus, and that small DNA-binding molecules promote the disintegration of paraspeckles and other lncRNA condensates. Furthermore, we found that paraspeckles regulate the differentiation of hPSCs. CONCLUSIONS Positive correlation between the size of the nucleus and the number of paraspeckles exist in numerous types of human cells. The tethering and structure of paraspeckles, as well as other lncRNAs, to the genome can be disrupted by small molecules that intercalate in DNA. The structure-function relationship of lncRNAs that regulates stem cell differentiation is likely to be determined by the dynamics of nucleus size and binding site accessibility.

中文翻译：

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核的大小和DNA的可及性与细胞分化中散斑形成的调控有关。

背景技术许多长的非编码RNA（lncRNA）已经涉及一般的和细胞类型特异性的分子调节。在这里，我们询问了细胞中核lncRNA冷凝物看似随机出现的基本基础是什么，我们寻求了可以促进lncRNA冷凝物在体内分解的化合物。结果作为比较不同细胞类型的lncRNA和细胞特性的基础，我们筛选了人类多能干细胞（hPSC）中的lncRNA，这些多能干细胞已分化为细胞谱系图谱。我们发现，通过lncRNA NEAT1的聚集形成的副斑点被细胞核的大小所缩放，并且小的DNA结合分子促进副斑点和其他lncRNA缩合物的分解。此外，我们发现散斑调节hPSCs的分化。结论在许多类型的人类细胞中，核的大小与散斑的数量之间存在正相关。散斑以及其他lncRNA与基因组的系留和结构可能会被嵌入DNA中的小分子破坏。调节干细胞分化的lncRNA的结构-功能关系可能由细胞核大小和结合位点可及性的动力学决定。