Characterizing isomiR variants within the micro RNA ‐34/449 family

miR‐34/449 micro RNA s are conserved regulators of multiciliated cell differentiation. Here, we evidence and characterize expression of two isomiR variant sequences from the miR‐34/449 family in human airway epithelial cells. These isomiRs differ from their canonical counterparts miR‐34b and miR‐449c by one supplemental uridine at their 5′‐end, leading to a one‐base shift in their seed region. Overexpression of canonical miR‐34/449 or 5′‐isomiR‐34/449 induces distinct gene expression profiles and biological effects. However, some target transcripts and functional activities are shared by both canonical micro RNA s and isomiRs. Indeed, both repress important targets that result in cell cycle blockage and Notch pathway inhibition. Our findings suggest that 5′‐isomiR‐34/449 may represent additional mechanisms by which miR‐34/449 family finely controls several pathways to drive multiciliogenesis.