Dataset Information

Developmentally regulated alternative splicing is perturbed in type 1 diabetic skeletal muscle.

ABSTRACT: INTRODUCTION: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. CONCLUSION:Embryonic spliced variants are inappropriately expressed in type 1 diabetic skeletal muscle. Muscle Nerve 56: 744-749, 2017.

SUBMITTER: Nutter CA

PROVIDER: S-EPMC5704903 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Developmentally regulated alternative splicing is perturbed in type 1 diabetic skeletal muscle.

Nutter Curtis A CA Jaworski Elizabeth E Verma Sunil K SK Perez-Carrasco Yareli Y Kuyumcu-Martinez Muge N MN

Muscle & nerve 20170417 4

<h4>Introduction</h4>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.<h4>Methods</h4>AS patterns were determined by reverse transcripti ...[more]

PMID: 28164326

Similar Datasets

Project description:Rationale: The adult skeletal muscle can self-repair efficiently following mechanical or pathological damage due to its remarkable regenerative capacity. However, regulatory mechanisms underlying muscle regeneration are complicated and have not been fully elucidated. Alternative splicing (AS) is a major mechanism responsible for post-transcriptional regulation. Many aberrant AS events have been identified in patients with muscular dystrophy which is accompanied by abnormal muscle regeneration. However, little is known about the correlation between AS and muscle regeneration. It has been reported that RNA binding motif protein 24 (Rbm24), a tissue-specific splicing factor, is involved in embryo myogenesis while the role of Rbm24 in adult myogenesis (also called muscle regeneration) is poorly understood. Methods: To investigate the role of Rbm24 in adult skeletal muscle, we generated Rbm24 conditional knockout mice and satellite cell-specific knockout mice. Furthermore, a cardiotoxin (CTX)-induced injury model was utilized to assess the effects of Rbm24 on skeletal muscle regeneration. Genome-wide RNA-Seq was performed to identify the changes in AS following loss of Rbm24. Results: Rbm24 knockout mice displayed abnormal regeneration 4 months after tamoxifen treatment. Using RNA-Seq, we found that Rbm24 regulated a complex network of AS events involved in multiple biological processes, including myogenesis, muscle regeneration and muscle hypertrophy. Moreover, using a CTX-induced injury model, we showed that loss of Rbm24 in skeletal muscle resulted in myogenic fusion and differentiation defects and significantly delayed muscle regeneration. Furthermore, satellite cell-specific Rbm24 knockout mice recapitulated the defects in regeneration seen in the global Rbm24 knockout mice. Importantly, we demonstrated that Rbm24 regulated AS of Mef2d, Naca, Rock2 and Lrrfip1 which are essential for myogenic differentiation and muscle regeneration. Conclusions: The present study demonstrated that Rbm24 regulates dynamic changes in AS and is essential for adult skeletal muscle regeneration.

Dataset Information

Developmentally regulated alternative splicing is perturbed in type 1 diabetic skeletal muscle.

Publications

Developmentally regulated alternative splicing is perturbed in type 1 diabetic skeletal muscle.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure