Long non-coding RNA GAS5 controls human embryonic stem cell self-renewal by maintaining NODAL signalling
Summary
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 |
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| Journal | Nature communications |
| Publication Date | 2016 Nov 4;7:13287 |
| PubMed | 27811843 |
| PubMed Central | PMC5097163 |
| DOI | 10.1038/ncomms13287 |