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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
MicroRNA-9 Modulates Hes1 ultradian oscillations by forming a double-negative feedback loop.
Cell Rep. 2, 10-18 (2012)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
ISSN (print) / ISBN
2211-1247
e-ISSN
2211-1247
Journal
Cell Reports
Quellenangaben
Volume: 2,
Issue: 1,
Pages: 10-18
Publisher
Cell Press
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Helmholtz Pioneer Campus (HPC)