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Frank, F, Kavousi, N, Bountali, A, Dammer, EB, Maarabouni, MM and Ortlund, E (2020) The lncRNA Growth Arrest Specific 5 regulates cell survival via distinct structural modules with independent functions. Cell Reports, 32 (3). ISSN 2211-1247
CELL-REPORTS-D-19-03803_R3.pdf - Accepted Version
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1-s2.0-S2211124720309141-main.pdf - Published Version
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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.
Item Type: | Article |
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Additional Information: | The final version of this article and all relevant information related to it can be found at; https://www.sciencedirect.com/science/article/pii/S2211124720309141?via%3Dihub |
Uncontrolled Keywords: | lncRNAs; SHAPE; RNA structure; cancer; GAS5 |
Subjects: | Q Science > Q Science (General) Q Science > QD Chemistry > QD415 Biochemistry R Medicine > R Medicine (General) R Medicine > R Medicine (General) > R735 Medical education. Medical schools. Research |
Divisions: | Faculty of Natural Sciences > School of Life Sciences |
Depositing User: | Symplectic |
Date Deposited: | 22 Jul 2020 15:08 |
Last Modified: | 17 Aug 2020 13:17 |
URI: | https://eprints.keele.ac.uk/id/eprint/8413 |