Amourda, C., Saunders, T.E. The mirtron miR-1010 functions in concert with its host gene SKIP to balance elevation of nAcRβ2. Sci Rep 10, 1688 (2020). https://doi.org/10.1038/s41598-020-58655-7
Mirtrons are non-canonical miRNAs arising by splicing and debranching from short introns. A plethora of introns have been inferred by computational analyses as potential mirtrons. Yet, few have been experimentally validated and their functions, particularly in relation to their host genes, remain poorly understood. Here, we found that Drosophila larvae lacking either the mirtron miR-1010 or its binding site in the nicotinic acetylcholine receptor β2 (nAcRβ2) 3′UTR fail to grow properly and pupariate. Increase of cortical nAcRβ2 mediated by neural activity elevates the level of intracellular Ca2+, which in turn activates CaMKII and, further downstream, the transcription factor Adf-1. We show that miR-1010 downregulates nAcRβ2. We reveal that Adf-1 initiates the expression of SKIP, the host gene of miR-1010. Preventing synaptic potentials from overshooting their optimal range requires both SKIP to temper synaptic potentials (incoherent feedforward loop) and miR-1010 to reduce nAcRβ2 mRNA levels (negative feedback loop). Our results demonstrate how a mirtron, in coordination with its host gene, contributes to maintaining appropriate receptor levels, which in turn may play a role in maintaining homeostasis.
This work was supported by the National Research Foundation Singapore under an NRF Fellowship to T.E.S. (NRF2012NRF-NRFF001-094).