Control of antagonistic components of the hedgehog signaling pathway by microRNAs in Drosophila. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Genetics Année : 2008

Control of antagonistic components of the hedgehog signaling pathway by microRNAs in Drosophila.

Résumé

Hedgehog (Hh) signaling is critical for many developmental processes and for the genesis of diverse cancers. Hh signaling comprises a series of negative regulatory steps, from Hh reception to gene transcription output. We previously showed that stability of antagonistic regulatory proteins, including the coreceptor Smoothened (Smo), the kinesin-like Costal-2 (Cos2), and the kinase Fused (Fu), is affected by Hh signaling activation. Here, we show that the level of these three proteins is also regulated by a microRNA cluster. Indeed, the overexpression of this cluster and resulting microRNA regulation of the 3'-UTRs of smo, cos2, and fu mRNA decreases the levels of the three proteins and activates the pathway. Further, the loss of the microRNA cluster or of Dicer function modifies the 3'-UTR regulation of smo and cos2 mRNA, confirming that the mRNAs encoding the different Hh components are physiological targets of microRNAs. Nevertheless, an absence of neither the microRNA cluster nor of Dicer activity creates an hh-like phenotype, possibly due to dose compensation between the different antagonistic targets. This study reveals that a single signaling pathway can be targeted at multiple levels by the same microRNAs.

Dates et versions

hal-00319091 , version 1 (05-09-2008)

Identifiants

Citer

Florence Friggi-Grelin, Laurence Lavenant-Staccini, Pascal Therond. Control of antagonistic components of the hedgehog signaling pathway by microRNAs in Drosophila.. Genetics, 2008, 179 (1), pp.429-39. ⟨10.1534/genetics.107.083733⟩. ⟨hal-00319091⟩
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