Frank, F, Kavousi, N, Bountali, A, Dammer, EB, Maarabouni, MM ORCID: https://orcid.org/0000-0001-8324-1325 and Ortlund, E (2020) The lncRNA Growth Arrest Specific 5 regulates cell survival via distinct structural modules with independent functions. Cell Reports, 32 (3).

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CELL-REPORTS-D-19-03803_R3.pdf - Accepted 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
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

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