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Abstract:
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.