microRNAs are small non-coding RNAs which form a silencing complex (miRISC) in association with Argonaute proteins (ALG-1/2). These complexes specifically bind messenger RNA (mRNA) 3' untranslated regions (3' UTR) in order to regulate gene expression. microRNAs are involved in the regulation of genes implicated in cell proliferation and differentiation. Deregulation of the cellular level of microRNAs has been shown to contribute to cancer development. It is therefore essential for cells to control microRNA production and degradation.A previous study in our laboratory identified DCS-1, the human ortholog of decapping scavenger enzyme DcpS, in complex with XRN-1 (5'-3' exonuclease), as an important regulator of microRNA level in C. elegans (Bosse et al, Mol. Cell, 2013). From this work, we identified a new degradation complex which is involved in the microRNA regulation but it is still unclear how microRNAs are selected and targeted for degradation by this complex.To gain some insights about microRNAs regulation, we identified components of the DCS-1 degradation complex using mass spectrometry. Among the interactors, we found the type 2C phosphatase PPM-2. The loss of
ppm-2 induces several developmental defect which are associated with the loss of microRNAs.
ppm-2 genetically interacts with the
let-7 microRNA family by enhancing the defects observed in these mutant animals. We further observed that the loss of
ppm-2 abrogates the gene silencing induced by
let-7. At the molecular level, mature microRNAs are downregulated in
ppm-2 mutant animals. While key components of the miRISC and degradation complex are not affected in this mutant animal, we observe a defect in the release of microRNAs from the miRISC.Taken together our results suggest that PPM-2 is required for the release of the microRNAs from the silencing complex.