title: The RNA-binding protein Arrest (Bruno) regulates alternative splicing to enable myofibril maturation in Drosophila flight muscle.
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.
authors.affiliation: Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Spletter
authors.affiliation: Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Barz
authors.affiliation: Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Assa
authors.initials: A
authors.lastname: Yeroslaviz
authors.affiliation: Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schönbauer
authors.affiliation: Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Irene R S
authors.initials: IR
authors.lastname: Ferreira
authors.affiliation: Max Planck Institute of Cell Biology and Genetics, Dresden, Germany.
authors.forename: Mihail
authors.initials: M
authors.lastname: Sarov
authors.affiliation: Research Institute of Molecular Pathology (IMP) Vienna Biocenter (VBC), Vienna, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gerlach
authors.affiliation: Research Institute of Molecular Pathology (IMP) Vienna Biocenter (VBC), Vienna, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Stark
authors.affiliation: Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Bianca H
authors.initials: BH
authors.lastname: Habermann
authors.affiliation: Max Planck Institute of Biochemistry, Martinsried, Germany schnorrer@biochem.mpg.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Schnorrer
mesh_terms: D017398:Alternative Splicing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster; D018482:Muscle, Skeletal / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D016601:RNA-Binding Proteins; C093437:bru1 protein, Drosophila
keywords: Arrest; Drosophila; alternative splicing; flight muscle; myofibril