MicroRNAs (miRNAs) critically modulate stem cell pluripotency, but the precise mechanistic mechanism remains largely unknown. This study systematically reveals the general mechanistic roles of miRNAs in mouse stem cells by analyzing global physical interactions between miRNAs and their targets. Generally, miRNAs primarily repress developmental processes, but surprisingly the top up-regulated miRNAs do not directly target the pluripotent core factors as thought; they only target extrinsic signal pathways associated with pluripotency. This suggested that the most important miRNAs in stem cells may only indirectly regulate the pluripotency via the genetic system . Interestingly, miRNAs predominately target and repress DNA methyltransferase, core enzymes for DNA methylation, and decreasing methylation in turn activates the top miRNAs. This system-wide circuit between up-regulated miRNAs and the repressed DNA methylation system would eventually activate pluripotent core factors for pluripotency. Therefore, miRNAs systematically repress development and inhibit the epigenetic system to  modulate stem cell pluripotency.
MicroRNAs (miRNAs) critically modulate stem cell pluripotency, but the fundamental mechanism remains largely unknown. This study systematically reveals the global mechanism of miRNA functions in mouse stem cells by analyzing genome-wide physical interactions between miRNAs and their targets. Generally, miRNAs primarily repress developmental processes, but surprisingly the top up-regulated miRNAs do not directly target the pluripotent core factors as thought; they only target the signal pathways associated with pluripotency. This suggests that the most important miRNAs in stem cells may only indirectly regulate the pluripotency . Interestingly, miRNAs predominately target and repress DNA methyltransferases, the core enzymes for DNA methylation, and decreasing methylation in turn activates the top miRNAs. This system-wide circuit between up-regulated miRNAs and the repressed DNA methylation system eventually activates the pluripotent core factors for pluripotency. Therefore, miRNAs systematically repress development and inhibit the epigenetic system to dynamically modulate stem cell pluripotency.
R
precise mechanistic
fundamental
R
general mechanistic roles of miRNAs
global mechanism of miRNA functions
R
global
genome-wide
R
extrinsic
the
R
suggested
suggests
D
via the genetic system
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methyltransferase,
methyltransferases, the
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would eventually activate
eventually activates the
A
dynamically