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Cell Rep July 26, 2012; 2 (1): 10-8.

MicroRNA-9 Modulates Hes1 ultradian oscillations by forming a double-negative feedback loop.

Bonev B , Stanley P , Papalopulu N .

Short-period (ultradian) oscillations of Hes1, a Notch signaling effector, are essential for maintaining neural progenitors in a proliferative state, while constitutive downregulation of Hes1 leads to neuronal differentiation. Hes1 oscillations are driven by autorepression, coupled with high instability of the protein and mRNA. It is unknown how Hes1 mRNA stability is controlled and furthermore, how cells exit oscillations in order to differentiate. Here, we identify a microRNA, miR-9, as a component of ultradian oscillations. We show that miR-9 controls the stability of Hes1 mRNA and that both miR-9 overexpression and lack of miR-9 dampens Hes1 oscillations. Reciprocally, Hes1 represses the transcription of miR-9, resulting in out-of-phase oscillations. However, unlike the primary transcript, mature miR-9 is very stable and thus accumulates over time. Given that raising miR-9 levels leads to dampening of oscillations, these findings provide support for a self-limiting mechanism whereby cells might terminate Hes1 oscillations and differentiate.

PubMed ID: 22840391
PMC ID: PMC4103481
Article link: Cell Rep
Grant support: [+]

Species referenced: Xenopus
Genes referenced: gnl3 hes1 mmut notch1 sox3 tbx2 tcf3
Antibodies: Sox3 Ab2

Article Images: [+] show captions
References [+] :
Ali, Cell cycle-regulated multi-site phosphorylation of Neurogenin 2 coordinates cell cycling with differentiation during neurogenesis. 2011, Pubmed, Xenbase