miR-34/449 control apical actin network formation during multiciliogenesis through small GTPase pathways

Area of Science:

• Cell Biology
• Developmental Biology
• Molecular Biology

Background:

• Vertebrate multiciliated cells (MCCs) propel fluids.
• The miR-34/449 family initiates MCC differentiation by repressing cell cycle and Notch pathways.

Purpose of the Study:

• Investigate the later roles of miR-34/449 in MCC differentiation.
• Identify molecular mechanisms regulating basal body anchoring and actin network assembly.

Main Methods:

• Utilized human and Xenopus multiciliated cells.
• Identified microRNA targets using bioinformatics and molecular assays.
• Assessed the impact of messenger RNA protection on actin cap formation and multiciliogenesis.

Main Results:

• miR-34/449 promote apical actin network assembly for basal body anchoring.
• R-Ras was identified as a key regulator, targeted by miR-34/449.
• Impaired R-Ras regulation by miR-34/449 disrupted actin cap formation and multiciliogenesis.
• miR-34/449 facilitate Filamin-A relocalization near basal bodies.

Conclusions:

• miR-34/449 play a multifaceted role in MCC differentiation beyond initial cell cycle repression.
• These microRNAs coordinate actin network formation and basal body anchoring via R-Ras and Filamin-A.
• The study highlights the intricate regulation of complex differentiation programs by microRNAs.