Proteomics

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The lncRNA Growth Arrest Specific 5 regulates cell survival via distinct structural modules with independent functions


ABSTRACT: There is increasing evidence that the architecture of long non-coding RNAs – 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 used SHAPE-MaP to probe the structure of Gas5 in vitro and in cellulo. The results show that Gas5 contains three separate structural modules including the previously predicted steroid receptor binding hairpin motif. Functional assays show that the newly identified modules 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 mTOR inhibition on cell growth. Disruption of specific secondary structures within the modules abolish their function in cells. These results highlight the central role of Gas5 in regulating cell survival and reveals how a single lncRNA transcript utilizes a modular structure-function relationship to respond to a variety of cellular stresses under various cellular conditions.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Duc Duong  

LAB HEAD: Eric Ortlund

PROVIDER: PXD018584 | Pride | 2021-04-07

REPOSITORIES: Pride

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Publications

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

Frank Filipp F   Kavousi Nadieh N   Bountali Aikaterini A   Dammer Eric B EB   Mourtada-Maarabouni Mirna M   Ortlund Eric A EA  

Cell reports 20200701 3


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 structura  ...[more]

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