The lncRNA Growth Arrest Specific 5 Regulates Cell Survival via Distinct Structural Modules with Independent Functions

Mourtada-Maarabouni, Mirna

Abstract

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.

Citation

Frank, F., Kavousi, N., Bountali, A., B. Dammer, E., Mourtada-Maarabouni, M., & A. Ortlund, E. (2020). The lncRNA Growth Arrest Specific 5 Regulates Cell Survival via Distinct Structural Modules with Independent Functions. Cell Reports, https://doi.org/10.1016/j.celrep.2020.107933

• Journal Article Type: Article
• Acceptance Date: Jun 22, 2020
• Online Publication Date: Jul 21, 2020
• Publication Date: Jul 21, 2020
• Publicly Available Date: May 26, 2023
• Journal: Cell Reports
• Print ISSN: 2211-1247
• Publisher: Cell Press
• DOI: https://doi.org/10.1016/j.celrep.2020.107933
• Keywords: lncRNAs; SHAPE; RNA structure; cancer; GAS5
• Publisher URL: https://doi.org/10.1016/j.celrep.2020.107933