AGO1 homeostasis involves differential production of 21-nt and 22-nt miR168 species by MIR168a and MIR168b.

• Main Author: Hervé Vaucheret
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2009-07-01
• Series: PLoS ONE
• Online Access: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19649244/pdf/?tool=EBI

<h4>Background</h4>AGO1 associates with microRNAs (miRNAs) and regulates mRNAs through cleavage and translational repression. AGO1 homeostasis entails DCL1-dependent production of miR168 from MIR168a and MIR168b transcripts, post-transcriptional stabilization of miR168 by AGO1, and AGO1-catalyzed miR168-guided cleavage of AGO1 mRNA.<h4>Principal findings</h4>This study reveals that MIR168a is highly expressed and predominantly produces a 21-nt miR168 species. By contrast, MIR168b is expressed at low levels and produces an equal amount of 21- and 22-nt miR168 species. Only the 21-nt miR168 is preferentially stabilized by AGO1, and consequently, the accumulation of the 22-nt but not the 21-nt miR168 is reduced when DCL1 activity is impaired. mir168a mutants with strongly reduced levels of 21-nt miR168 are viable but exhibit developmental defects, particularly during environmentally challenging conditions.<h4>Conclusions/significance</h4>These results suggest that 22-nt miR168 ensures basal cleavage of AGO1 mRNA whereas 21-nt miR168 permits an effective response to endogenous or environmental fluctuations owing to its preferential stabilization by AGO1.