2023年11月6日，《自然—细胞生物学》杂志发表了日本科学家的一项最新研究成果。大阪大学Tetsuro Hirose等研究人员合作发现，由lncRNA NEAT1结构域指定的外壳蛋白组成决定作为独特无膜细胞器的旁斑形成。

研究人员报道了由NEAT1_2长非编码RNA搭架的具有核壳结构的旁斑作为不同无膜细胞器（MLO）存在的分子机制。研究人员发现了NEAT1基因缺失突变体，这些突变体能组装出并入核斑的旁斑。包括SFPQ、HNRNPF和BRG1在内的几种旁斑蛋白阻止了这种结合，从而促进了旁斑与核斑的分离。这些蛋白质在旁斑中的壳定位由NEAT1_2长非编码RNA结构域决定，是这一分离过程所需的。相反，与U2相关的剪接体蛋白参与了将旁斑内化为核斑的过程。

这项研究表明，旁斑壳的组成决定了MLO在细胞核中的独立性，为人们深入了解壳在定义MLO的特征和功能方面的重要性提供了启示。

研究人员表示，许多通过相分离形成的MLO在各种细胞过程中发挥着至关重要的作用。尽管这些无膜细胞器共存于细胞中，但它们是如何在不凝聚或不被吞噬的情况下保持其独立性的，在很大程度上仍是未知数。

附：英文原文

Title: Shell protein composition specified by the lncRNA NEAT1 domains dictates the formation of paraspeckles as distinct membraneless organelles

Author: Takakuwa, Hiro, Yamazaki, Tomohiro, Souquere, Sylvie, Adachi, Shungo, Yoshino, Hyura, Fujiwara, Naoko, Yamamoto, Tetsuya, Natsume, Tohru, Nakagawa, Shinichi, Pierron, Gerard, Hirose, Tetsuro

Issue&Volume: 2023-11-06

Abstract: Many membraneless organelles (MLOs) formed through phase separation play crucial roles in various cellular processes. Although these MLOs co-exist in cells, how they maintain their independence without coalescence or engulfment remains largely unknown. Here, we investigated the molecular mechanism by which paraspeckles with core–shell architecture scaffolded by NEAT1_2 long noncoding RNAs exist as distinct MLOs. We identified NEAT1 deletion mutants that assemble paraspeckles that are incorporated into nuclear speckles. Several paraspeckle proteins, including SFPQ, HNRNPF and BRG1, prevent this incorporation and thus contribute to the segregation of paraspeckles from nuclear speckles. Shell localization of these proteins in the paraspeckles, which is determined by NEAT1_2 long noncoding RNA domains, is required for this segregation process. Conversely, U2-related spliceosomal proteins are involved in internalizing the paraspeckles into nuclear speckles. This study shows that the paraspeckle shell composition dictates the independence of MLOs in the nucleus, providing insights into the importance of the shell in defining features and functions of MLOs. Takakuwa, Yamazaki et al. show that the long noncoding RNA NEAT1 domains specify a set of proteins that localize to the outer shell and distinguish nuclear speckles from paraspeckles to preserve their structural identity.

DOI: 10.1038/s41556-023-01254-1

Source: https://www.nature.com/articles/s41556-023-01254-1