© 2014 The Authors. Published under the terms of the CC BY NC ND 4.0 license. In Drosophila, fibrillar flight muscles (IFMs) 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 IFMs. 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. Synopsis Arrest (Bruno) regulates flight muscle-specific splicing of a large number of genes encoding for sarcomeric proteins. Correct expression of these flight muscle-specific isoforms is essential to build the contractile apparatus of fibrillar flight muscles. Spalt major induces expression of the RNA binding protein Arrest in flight muscles. Arrest induces fibrillar muscle-specific splicing of sarcomeric protein isoforms in flight muscles. Arrest is essential for normal myofibril maturation and sarcomere growth to prevent hyper-contraction in adult flight muscles. Arrest (Bruno) regulates flight muscle-specific splicing of a large number of genes encoding for sarcomeric proteins. Correct expression of these flight muscle-specific isoforms is essential to build the contractile apparatus of fibrillar flight muscles.
Spletter, M. L., Barz, C., Yeroslaviz, A., Schönbauer, C., Ferreira, I. R. S., Sarov, M., … Schnorrer, F. (2015). The RNA ‐binding protein Arrest (Bruno) regulates alternative splicing to enable myofibril maturation in Drosophila flight muscle . EMBO Reports, 16(2), 178–191. https://doi.org/10.15252/embr.201439791