Developmentally regulated alternative splicing is perturbed in type 1 diabetic skeletal muscle.
BACKGROUND
Type 1 diabetic patients can develop skeletal muscle weakness and atrophy by molecular mechanisms that are not well understood. Alternative splicing (AS) is critical for gene expression in the skeletal muscle, and its dysregulation is implicated in muscle weakness and atrophy. Therefore, we investigated whether AS patterns are affected in type 1 diabetic skeletal muscle contributing to skeletal muscle defects.


METHODS
AS patterns were determined by reverse transcription-polymerase chain reaction and levels of RNA binding proteins were assessed by Western blot in type 1 diabetic mouse skeletal muscle and during normal mouse skeletal muscle development.


RESULTS
Five genes with critical functions in the skeletal muscle are misspliced in type 1 diabetic skeletal muscle, resembling their AS patterns at embryonic stages. AS of these genes undergoes dramatic transitions during skeletal muscle development, correlating with changes in specific RNA binding proteins.


CONCLUSIONS
Embryonic spliced variants are inappropriately expressed in type 1 diabetic skeletal muscle. Muscle Nerve 56: 744-749, 2017.
Biochemistry and Molecular Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas, 77555, USA.
Curtis A
CA
Nutter
Biochemistry and Molecular Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas, 77555, USA.
Elizabeth
http://orcid.org/0000-0002-4886-0451
E
Jaworski
Biochemistry and Molecular Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas, 77555, USA.
Sunil K
SK
Verma
Department of Biology, University of Texas, Arlington, Texas, USA.
Yareli
Y
Perez-Carrasco
Biochemistry and Molecular Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas, 77555, USA.|Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas, USA.|Institute for Translational Sciences University of Texas Medical Branch, Galveston, Texas, USA.
Muge N
MN
Kuyumcu-Martinez
D017398:Alternative Splicing / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D016688:Mice, Inbred NOD; D018482:Muscle, Skeletal / Q000196:embryology* / Q000254:growth & development*
RNA binding proteins; alternative splicing; muscle development; skeletal muscle; type 1 diabetes