Department of Neurology, University of Massachusetts Medical School, 55 Lake Ave. North, Worcester, MA, 01655, USA.
Department of Neurology, University of Massachusetts Medical School, 55 Lake Ave. North, Worcester, MA, 01655, USA.
Curr Opin Cell Biol. 2020 Jun;64:67-76. doi: 10.1016/j.ceb.2020.02.015. Epub 2020 Apr 4.
RNAs play diverse roles in formation and function of subnuclear compartments, most of which are associated with active genes. NEAT1 and NEAT2/MALAT1 exemplify long non-coding RNAs (lncRNAs) known to function in nuclear bodies; however, we suggest that RNA biogenesis itself may underpin much nuclear compartmentalization. Recent studies show that active genes cluster with nuclear speckles on a genome-wide scale, significantly advancing earlier cytological evidence that speckles (aka SC-35 domains) are hubs of concentrated pre-mRNA metabolism. We propose the 'karyotype to hub' hypothesis to explain this organization: clustering of genes in the human karyotype may have evolved to facilitate the formation of efficient nuclear hubs, driven in part by the propensity of ribonucleoproteins (RNPs) to form large-scale condensates. The special capacity of highly repetitive RNAs to impact architecture is highlighted by recent findings that human satellite II RNA sequesters factors into abnormal nuclear bodies in disease, potentially co-opting a normal developmental mechanism.
RNAs 在亚核区室的形成和功能中发挥着多样化的作用，其中大多数与活性基因相关。NEAT1 和 NEAT2/MALAT1 是众所周知的在核体中发挥作用的长非编码 RNA（lncRNA）的范例；然而，我们认为 RNA 生物发生本身可能是许多核区室化的基础。最近的研究表明，活性基因在全基因组范围内与核斑点聚集在一起，这大大推进了早期细胞学证据，表明斑点（又名 SC-35 结构域）是浓缩前体 RNA 代谢的中心。我们提出“核型到中心”假说来解释这种组织：人类核型中基因的聚类可能是为了促进有效的核中心的形成而进化的，部分原因是核糖核蛋白（RNP）形成大规模凝聚物的倾向。高度重复的 RNA 对结构产生影响的特殊能力，突出体现在最近的发现中，即人类卫星 II RNA 将因子隔离到疾病中的异常核体中，可能利用了正常的发育机制。
