Institute of Stem Cell Research (ISF), Helmholtz Zentrum München, Neuherberg, Germany.
Institute of Stem Cell Research (ISF), iPSC Core Facility, Helmholtz Zentrum München, Neuherberg, Germany.
BMC Biol. 2020 Apr 22;18(1):42. doi: 10.1186/s12915-020-00770-y.
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.
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.
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.
许多长非编码 RNA（lncRNA）参与了一般和细胞类型特异性的分子调控。在这里，我们想知道是什么构成了核 lncRNA 凝聚物在细胞中随机出现的基本基础，并寻找可以促进 lncRNA 凝聚物在体内解体的化合物。
作为在不同细胞类型中比较 lncRNA 和细胞特性的基础，我们筛选了分化为细胞谱系图谱的人多能干细胞（hPSC）中的 lncRNA。我们发现，由 lncRNA NEAT1 聚集形成的核周斑是由核的大小决定的，并且小的 DNA 结合分子促进核周斑和其他 lncRNA 凝聚物的解体。此外，我们发现核周斑调节 hPSC 的分化。
在许多类型的人类细胞中，核的大小与核周斑的数量之间存在正相关关系。核周斑以及其他 lncRNA 与基因组的连接和结构可以被嵌入 DNA 的小分子破坏。调节干细胞分化的 lncRNA 的结构-功能关系可能由核大小和结合位点可及性的动态决定。
