Regulation of atrophin by both strands of the mir-8 precursor

In Drosophila melanogaster, miR-8-3p regulates mRNA levels of atrophin, a factor involved in neuromotor coordination, and we found that Blattella germanica with suppressed atrophin showed motor problems. Bionformatic predictions and luciferase-reporter tests indicated that B.germanica atrophin mRNA contains target sites for miR-8-3p and miR-8-5p. Suppression of miR-8-3p or miR-8-5p appeared to increase atrophin mRNA. The effects of suppression of Argonaute (AGO) 1 or AGO2 expression on miR-8-3p and miR-8-5p suggested that miR-8-3-p might predominantly bind to AGO1, whereas miR-8-5p might bind to a moderate extent to both AGO1 and AGO2 in the respective RNA-induced silencing complexes (RISCs). We propose that the interplay of miR-8-3p, miR-8-5p, AGO1 and AGO2, maintain the appropriate levels of atrophin mRNA. This would be the first example of two strands of the same miRNA precursor regulating a single transcript. © 2013 Elsevier Ltd.Support for this research was provided by the Spanish Spanish Ministry of Science and Innovation (grant CGL2008-03517/BOS to X.B.; BFU2010-21123 and CSD2007-00008 to M.M.), by FEDER funds, and by the CSIC (grant 2010TW0019, from the Formosa program, to X.B. and a predoctoral fellowship to M.R. from the JAE program). M.M. is an ICREA Research Professor.Peer Reviewe