Long non-coding RNA GAS5 controls human embryonic stem cell self-renewal by maintaining NODAL signalling


Long non-coding RNAs (lncRNAs) are known players in the regulatory circuitry of the self-renewal in human embryonic stem cells (hESCs). However, most hESC-specific lncRNAs remain uncharacterized. Here we demonstrate that growth-arrest-specific transcript 5 (GAS5), a known tumour suppressor and growth arrest-related lncRNA, is highly expressed and directly regulated by pluripotency factors OCT4 and SOX2 in hESCs. Phenotypic analysis shows that GAS5 knockdown significantly impairs hESC self-renewal, but its overexpression significantly promotes hESC self-renewal. Using RNA sequencing and functional analysis, we demonstrate that GAS5 maintains NODAL signalling by protecting NODAL expression from miRNA-mediated degradation. Therefore, we propose that the above pluripotency factors, GAS5 and NODAL form a feed-forward signalling loop that maintains hESC self-renewal. As this regulatory function of GAS5 is stem cell specific, our findings also indicate that the functions of lncRNAs may vary in different cell types due to competing endogenous mechanisms.

Authors Xu C, Zhang Y, Wang Q, Xu Z, Jiang J, Gao Y, Gao M, Kang J, Wu M, Xiong J, Ji K, Yuan W, Wang Y, Liu H
Journal Nature communications
Publication Date 2016 Nov 4;7:13287
PubMed 27811843
PubMed Central PMC5097163
DOI 10.1038/ncomms13287

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