Sam68 splicing regulation contributes to motor unit establishment in the postnatal skeletal muscle

Elisa De Paola, Laura Forcina, Laura Pelosi, Simona Pisu, Piergiorgio La Rosa, Eleonora Cesari, Carmine Nicoletti, Luca Madaro, Neri Mercatelli, Filippo Biamonte, Annalisa Nobili, Marcello D'Amelio, Marco De Bardi, Elisabetta Volpe, Daniela Caporossi, Claudio Sette, Antonio Musarò, Maria Paola Paronetto

Research output: Contribution to journalArticlepeer-review

Abstract

RNA-binding proteins orchestrate the composite life of RNA molecules and impact most physiological processes, thus underlying complex phenotypes. The RNA-binding protein Sam68 regulates differentiation processes by modulating splicing, polyadenylation, and stability of select transcripts. Herein, we found that Sam68-/- mice display altered regulation of alternative splicing in the spinal cord of key target genes involved in synaptic functions. Analysis of the motor units revealed that Sam68 ablation impairs the establishment of neuromuscular junctions and causes progressive loss of motor neurons in the spinal cord. Importantly, alterations of neuromuscular junction morphology and properties in Sam68-/- mice correlate with defects in muscle and motor unit integrity. Sam68-/- muscles display defects in postnatal development, with manifest signs of atrophy. Furthermore, fast-twitch muscles in Sam68-/- mice show structural features typical of slow-twitch muscles, suggesting alterations in the metabolic and functional properties of myofibers. Collectively, our data identify a key role for Sam68 in muscle development and suggest that proper establishment of motor units requires timely expression of synaptic splice variants.

Original languageEnglish
Article numbere201900637
JournalLife Science Alliance
Volume3
Issue number10
DOIs
Publication statusPublished - Oct 2020

ASJC Scopus subject areas

  • Ecology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Plant Science
  • Health, Toxicology and Mutagenesis

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