Cell biology: Short RNAs and shortness of breath.

Abstract

The simultaneous deletion of six RNA molecules in mice has been found to cause respiratory and fertility defects, owing to improper assembly of structures called cilia on the cell surface. See Article p.115 The six microRNAs (miRNAs) of the miR-34/449 family are highly similar. Their functions overlap, so it is difficult to determine their specific biological roles. Lin He and colleagues present data obtained from mice deficient for all six miR-34/449 miRNAs. These animals exhibited frequent postnatal mortality, respiratory dysfunction — resembling respiratory complications seen in some patients with primary cilia dyskinesia — and infertility. The main underlying defects were shorter and fewer cilia in the cells of the respiratory tract, largely due to defects in basal body docking to the apical membrane. Of the 57 potential targets of miR-34/449 miRNAs that the authors identify, one is Cp110, a centriolar protein that suppresses cilia assembly. Interestingly, aberrant Cp110 levels in association with respiratory illness have already been uncovered.