The lncRNA Growth Arrest Specific 5 Regulates Cell Survival via Distinct Structural Modules with Independent Functions
The lncRNA Growth Arrest Specific 5 Regulates Cell Survival via Distinct Structural Modules with Independent Functions
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DOI：
10.1016/j.celrep.2020.107933
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发表时间：
2020-07-21
期刊：
影响因子：
8.8
通讯作者：
Ortlund, Eric A.
中科院分区：
文献类型：
--
作者：
Frank, Filipp;Kavousi, Nadieh;Ortlund, Eric A.
越来越多的证据表明，长链非编码rna （lncrna）的结构就像蛋白质的结构一样，在层次上被组织成具有不同功能的独立折叠子模块。然而，表征这些模块的细胞活动的研究很少。lncRNA生长阻滞特异性5 （GAS5）是应激和营养可用性下细胞存活的关键调节因子。我们使用SHAPE-MaP来探测GAS5的结构，并确定了在白血病T细胞中独立作用的三个独立的结构模块。低二级结构含量的5'端模块影响基础存活并减缓细胞周期，而高度结构化的核心模块介导哺乳动物雷帕霉素靶蛋白（mTOR）抑制细胞生长的作用。这些结果突出了GAS5在调节细胞存活中的核心作用，并揭示了单个lncRNA转录物如何利用模块化的结构-功能关系来响应各种细胞条件下的各种细胞应激。
There is increasing evidence that the architecture of long non-coding RNAs (lncRNAs) just like that of proteins-is hierarchically organized into independently folding sub-modules with distinct functions. Studies characterizing the cellular activities of such modules, however, are rare. The lncRNA growth arrest specific 5 (GAS5) is a key regulator of cell survival in response to stress and nutrient availability. We use SHAPE-MaP to probe the structure of GAS5 and identify three separate structural modules that act independently in leukemic T cells. The 5' terminal module with low secondary structure content affects basal survival and slows the cell cycle, whereas the highly structured core module mediates the effects of mammalian target of rapamycin (mTOR) inhibition on cell growth. These results highlight the central role of GAS5 in regulating cell survival and reveal how a single lncRNA transcript utilizes a modular structure-function relationship to respond to a variety of cellular stresses under various cellular conditions.