LncRNA OIP5-AS1/cyrano suppresses GAK expression to control mitosis.
LncRNA OIP5-AS1/cyrano suppresses GAK expression to control mitosis.
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lncRNA OIP5-AS1/Cyrano抑制GAK表达以控制有丝分裂。
DOI：
10.18632/oncotarget.17219
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发表时间：
2017-07-25
期刊：
影响因子：
--
通讯作者：
Gorospe M
中科院分区：
文献类型：
--
作者：
Kim J;Noh JH;Lee SK;Munk R;Sharov A;Lehrmann E;Zhang Y;Wang W;Abdelmohsen K;Gorospe M
一些长非编码 RNA (lncRNA) 可以调节基因表达程序，进而影响特定的细胞过程。我们试图确定细胞质中丰富的 lncRNA OIP5-AS1 抑制细胞增殖的机制。人宫颈癌 HeLa 细胞中 OIP5-AS1 的沉默引发了许多异常（单极、多极、错位）有丝分裂纺锤体的出现。通过结合拉下与 OIP5-AS1 结合的 mRNA 并鉴定 OIP5-AS1 沉默时差异表达的蛋白质的组合方法，我们鉴定了由 mRNA 编码的人类细胞周期调节蛋白子集，这些蛋白与 HeLa 细胞中的 OIP5-AS1 相互作用。进一步分析显示，GAK mRNA（编码对有丝分裂进展重要的细胞周期蛋白 G 相关激酶）与 OIP5-AS1 显着相关。这两个转录物之间的相互作用导致 GAK mRNA 稳定性和 GAK 蛋白丰度降低，正如在 OIP5-AS1 水平升高或降低的细胞中所确定的那样。重要的是，如果同时沉默 GAK，则沉默 OIP5-AS1 后出现的异常有丝分裂细胞分裂可部分得到恢复。这些发现表明，沉默 OIP5-AS1 后出现的异常有丝分裂是由 GAK 水平不合时宜的升高引起的，并表明 OIP5-AS1 至少部分通过降低 GAK 水平来抑制细胞增殖。
Some long noncoding RNAs (lncRNAs) can regulate gene expression programs, in turn affecting specific cellular processes. We sought to identify the mechanism through which the lncRNA OIP5-AS1, which is abundant in the cytoplasm, suppressed cell proliferation. Silencing of OIP5-AS1 in human cervical carcinoma HeLa cells triggered the appearance of many aberrant (monopolar, multipolar, misaligned) mitotic spindles. Through a combination of approaches to pull down mRNAs bound to OIP5-AS1 and identify proteins differentially expressed when OIP5-AS1 was silenced, we identified a subset of human cell cycle regulatory proteins encoded by mRNAs that interacted with OIP5-AS1 in HeLa cells. Further analysis revealed that GAK mRNA, which encodes a cyclin G-associated kinase important for mitotic progression, associated prominently with OIP5-AS1. The interaction between these two transcripts led to a reduction in GAK mRNA stability and GAK protein abundance, as determined in cells in which OIP5-AS1 levels were increased or decreased. Importantly, the aberrant mitotic cell division seen after silencing OIP5-AS1 was partly rescued if GAK was simultaneously silenced. These findings indicate that the abnormal mitoses seen after silencing OIP5-AS1 were caused by an untimely rise in GAK levels and suggest that OIP5-AS1 suppresses cell proliferation at least in part by reducing GAK levels.
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影响因子：
11.8
作者：
Chen, XB
通讯作者：
Chen, XB
影响因子：
10.5
作者：
Cabili, Moran N.;Trapnell, Cole;Rinn, John L.
通讯作者：
Rinn, John L.
影响因子：
64.8
作者：
Gong, Chenguang;Maquat, Lynne E.
通讯作者：
Maquat, Lynne E.
lncRNA OIP5-AS1/Cyrano海绵RNA结合蛋白HUR。
影响因子：
14.9
作者：
Kim J;Abdelmohsen K;Yang X;De S;Grammatikakis I;Noh JH;Gorospe M
通讯作者：
Gorospe M
影响因子：
64.8
作者：
Royle, SJ;Bright, NA;Lagnado, L
通讯作者：
Lagnado, L