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In  Drosophila , fibrillar flight muscles ( IFM s) enable flight, while tubular muscles mediate other body movements. Here, we use  RNA ‐sequencing and isoform‐specific reporters to show that  spalt major  ( salm ) determines fibrillar muscle physiology by regulating transcription and alternative splicing of a large set of sarcomeric proteins. We identify the  RNA ‐binding protein Arrest (Aret, Bruno) as downstream of  salm . Aret shuttles between the cytoplasm and nuclei and is essential for myofibril maturation and sarcomere growth of  IFM s. Molecularly, Aret regulates  IFM ‐specific splicing of various  salm ‐dependent sarcomeric targets, including  Stretchin  and  wupA  (TnI), and thus maintains muscle fiber integrity. As Aret and its sarcomeric targets are evolutionarily conserved, similar principles may regulate mammalian muscle morphogenesis.

The RNA ‐binding protein Arrest (Bruno) regulates alternative splicing to enable myofibril maturation in Drosophila flight muscle