期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms9386
关键词
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资金
- CNRS
- French Government (National Research Agency, ANR) through the 'Investments for the Future' LABEX SIGNALIFE [ANR-11-LABX-0028-01]
- French Government (National Research Agency, ANR) through the FRANCE GENOMIQUE [ANR-10-Infra-01]
- ANR (MERCi) [ANR-09-GENO-039]
- ANR (COMMIT) [ANR-11-BSV2-021]
- ANR (MITHRA) [ANR-12-EMMA-0015-01]
- Vaincre la Mucoviscidose
- FRM [DEQ20130326464]
- Region PACA (Canceropole) [CG06]
- Agence Nationale de la Recherche (ANR) [ANR-12-EMMA-0015] Funding Source: Agence Nationale de la Recherche (ANR)
Vertebrate multiciliated cells (MCCs) contribute to fluid propulsion in several biological processes. We previously showed that microRNAs of the miR-34/449 family trigger MCC differentiation by repressing cell cycle genes and the Notch pathway. Here, using human and Xenopus MCCs, we show that beyond this initial step, miR-34/449 later promote the assembly of an apical actin network, required for proper basal bodies anchoring. Identification of miR-34/449 targets related to small GTPase pathways led us to characterize R-Ras as a key regulator of this process. Protection of RRAS messenger RNA against miR-34/449 binding impairs actin cap formation and multiciliogenesis, despite a still active RhoA. We propose that miR-34/449 also promote relocalization of the actin binding protein Filamin-A, a known RRAS interactor, near basal bodies in MCCs. Our study illustrates the intricate role played by miR-34/449 in coordinating several steps of a complex differentiation programme by regulating distinct signalling pathways.
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