RT Journal Article
SR Electronic
T1 Sam68 splicing regulation contributes to motor unit establishment in the postnatal skeletal muscle
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900637
DO 10.26508/lsa.201900637
VO 3
IS 10
A1 Elisa De Paola
A1 Laura Forcina
A1 Laura Pelosi
A1 Simona Pisu
A1 Piergiorgio La Rosa
A1 Eleonora Cesari
A1 Carmine Nicoletti
A1 Luca Madaro
A1 Neri Mercatelli
A1 Filippo Biamonte
A1 Annalisa Nobili
A1 Marcello D’Amelio
A1 Marco De Bardi
A1 Elisabetta Volpe
A1 Daniela Caporossi
A1 Claudio Sette
A1 Antonio Musarò
A1 Maria Paola Paronetto
YR 2020
UL https://www.life-science-alliance.org/content/3/10/e201900637.abstract
AB 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.