Journal Article

MiR-2 family regulates insect metamorphosis by controlling the juvenile hormone signaling pathway

Lozano, Jesus, Belles, Xavier, Montañez, Raúl

2015

Overview

In 2009 we reported that depletion of Dicer-1, the enzyme that catalyzes the final step of miRNA biosynthesis, prevents metamorphosis in Blattella germanica . However, the precise regulatory roles of miRNAs in the process have remained elusive. In the present work, we have observed that Dicer-1 depletion results in an increase of mRNA levels of Krúñíóüüüppel homolog 1 (Kr-h1), a juvenile hormone-dependent transcription factor that represses metamorphosis, and that depletion of Kr-h1 expression in Dicer-1 knockdown individuals rescues metamorphosis. We have also found that the 3′UTR of Kr-h1 mRNA contains a functional binding site for miR-2 family miRNAs (for miR-2, miR-13a, and miR-13b). These data suggest that metamorphosis impairment caused by Dicer-1 and miRNA depletion is due to a deregulation of Kr-h1 expression and that this deregulation is derived from a deficiency of miR-2 miRNAs. We corroborated this by treating the last nymphal instar of B. germanica with an miR-2 inhibitor, which impaired metamorphosis, and by treating Dicer-1-depleted individuals with an miR-2 mimic to allow nymphal-to-adult metamorphosis to proceed. Taken together, the data indicate that miR-2 miRNAs scavenge Kr-h1 transcripts when the transition from nymph to adult should be taking place, thus crucially contributing to the correct culmination of metamorphosis. Significance MicroRNAs are short, single-stranded RNAs that bind to target mRNAs and block their translation. Five years ago we observed in the cockroach Blattella germanica that general depletion of microRNAs prevents metamorphosis. This observation led to two key questions: Which microRNAs are involved in this action, and which target do they act on? The results reported herein show that the microRNAs involved are those of an miR-2 family (miR-2, miR-13a, and miR-13b), and the target is the transcription factor Krúñíóüppel homolog 1, a master repressor of insect metamorphosis. The data presented indicate that miR-2 microRNAs rapidly clear Krúñíóüüppel homolog 1 transcripts in the last nymphal instar, a process that is crucial for proper metamorphosis. This reveals the elegant mechanism of an miRNA family leading metamorphosis to its correct conclusion.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Algorithms / Animals / Binding Sites / Biological Sciences / Biosynthesis / Blattella germanica / Catalysis / Deregulation / DNA, Complementary - metabolism / Drosophila / Drosophila Proteins - metabolism / Enzymes / Female / Gene Expression Regulation, Developmental / Insect Proteins - metabolism / Insecta / Insects / instars / juvenile hormones / Juvenile Hormones - metabolism / messenger RNA / Metamorphosis / Metamorphosis, Biological / microRNA / MicroRNAs - metabolism / Phenotype / Protein expression / Ribonuclease III - metabolism / Ribonucleic acid / RNA / RNA Helicases - metabolism / Signal Transduction / Temperature / transcription factors / translation (genetics)