Long Noncoding RNA CRYBG3 Blocks Cytokinesis by Directly Binding G-Actin.
Long Noncoding RNA CRYBG3 Blocks Cytokinesis by Directly Binding G-Actin.
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长非编码 RNA CRYBG3 通过直接结合 G-肌动蛋白阻断细胞分裂
DOI：
10.1158/0008-5472.can-18-0988
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发表时间：
2018-08-15
期刊：
影响因子：
11.2
通讯作者：
Hei TK
中科院分区：
文献类型：
--
作者：
Pei H;Hu W;Guo Z;Chen H;Ma J;Mao W;Li B;Wang A;Wan J;Zhang J;Nie J;Zhou G;Hei TK
单体球状肌动蛋白 (G-肌动蛋白) 和聚合丝状肌动蛋白 (F-肌动蛋白) 之间的动态交换对于许多细胞过程（包括胞质分裂和维持基因组稳定性）至关重要。在这里，我们报道长非编码RNA LNC CRYBG3直接结合G-肌动蛋白，抑制其聚合和收缩环的形成，导致M期细胞停滞。肿瘤细胞中 LNC CRYBG3 的敲低增强了其恶性表型。全长 LNC CRYBG3 的核苷酸序列 228-237 和 β-肌动蛋白的 ser14 结构域对于它们的相互作用至关重要，并且这些位点中的任何一个的突变都会消除 LNC CRYBG3 与 G-肌动蛋白的结合。 LNC CRYBG3 与 G 肌动蛋白的结合阻断了 MAL 的核定位，从而使血清反应因子 (SRF) 远离几个立即早期基因的启动子区域，包括 JUNB 和 Arp3，这些基因是细胞增殖、肿瘤生长、粘附、运动和转移所必需的。这些发现揭示了一种新的 lncRNA-actin-MAL-SRF 通路，并强调 LNC CRYBG3 作为一种通过靶向肌动蛋白细胞骨架来阻断胞质分裂和治疗癌症的手段。
The dynamic interchange between monomeric globular actin (G-actin) and polymeric filamentous actin filaments (F-actin) is fundamental and essential to many cellular processes including cytokinesis and maintenance of genomic stability. Here we report that the long non-coding RNA LNC CRYBG3 directly binds G-actin to inhibit its polymerization and formation of contractile rings, resulting in M-Phase cell arrest. Knockdown of LNC CRYBG3 in tumor cells enhanced their malignant phenotypes. Nucleotide sequence 228–237 of the full-length LNC CRYBG3 and the ser14 domain of β-actin are essential for their interaction, and mutation of either of these sites abrogated binding of LNC CRYBG3 to G-actin. Binding of LNC CRYBG3 to G-actin blocked nuclear localization of MAL, which consequently kept serum response factor (SRF) away from the promoter region of several immediate early genes, including JUNB and Arp3, which are necessary for cellular proliferation, tumor growth, adhesion, movement, and metastasis. These findings reveal a novel lncRNA-actin-MAL-SRF pathway and highlight LNC CRYBG3 as a means to block cytokinesis and treat cancer by targeting the actin cytoskeleton.