Mesodermally expressed <i>Drosophila microRNA-1</i> is regulated by Twist and is required in muscles during larval growth

<jats:p>Although hundreds of evolutionarily conserved microRNAs have been discovered, the functions of most remain unknown. Here, we describe the embryonic spatiotemporal expression profile, transcriptional regulation, and loss-of-function phenotype of <jats:italic>Drosophila miR-1</jats:italic> (<jats:italic>DmiR-1</jats:italic>). <jats:italic>DmiR-1</jats:italic> RNA is highly expressed throughout the mesoderm of early embryos and subsequently in somatic, visceral, and pharyngeal muscles, and the dorsal vessel. The expression of <jats:italic>DmiR-1</jats:italic> is controlled by the Twist and Mef2 transcription factors. <jats:italic>DmiR-1<jats:sup>KO</jats:sup></jats:italic> mutants, generated using ends-in gene targeting, die as small, immobilized second instar larvae with severely deformed musculature. This lethality is rescued when a <jats:italic>DmiR-1</jats:italic> transgene is expressed specifically in the mesoderm and muscle. Strikingly, feeding triggers <jats:italic>DmiR-1<jats:sup>KO</jats:sup></jats:italic>-associated paralysis and death; starved first instar <jats:italic>DmiR-1<jats:sup>KO</jats:sup></jats:italic> larvae are essentially normal. Thus, <jats:italic>DmiR-1</jats:italic> is not required for the formation or physiological function of the larval musculature, but is required for the dramatic post-mitotic growth of larval muscle.</jats:p>