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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Nat+Commun
2016 ; 7
(ä): 13287
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Long non-coding RNA GAS5 controls human embryonic stem cell self-renewal by
maintaining NODAL signalling
#MMPMID27811843
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
Nat Commun
2016[Nov]; 7
(ä): 13287
PMID27811843
show ga
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.