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Loss of RNA-binding protein Sfpq causes long-gene transcriptopathy in skeletal muscle and severe muscle mass reduction with metabolic myopathy

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE106827 | GEO | 2019/03/18

REPOSITORIES: GEO

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Loss of RNA-Binding Protein Sfpq Causes Long-Gene Transcriptopathy in Skeletal Muscle and Severe Muscle Mass Reduction with Metabolic Myopathy.

Project description:Growing evidences are suggesting that extra-long genes in mammals are vulnerable for full-gene length transcription and dysregulation of long genes is a mechanism underlying human genetic disorders. How long-distance transcription is achieved is a fundamental question to be elucidated. In previous study, we had discovered that RNA-binding protein SFPQ preferentially binds to long pre-mRNAs and specifically regulates the cluster of neuronal genes >100 kbp. Here we investigated the roles of SFPQ for long gene expression, target specificities, and also physiological functions in skeletal muscle. Loss of Sfpq selectively downregulated genes >100 kbp including Dystrophin, which is 2.26 Mbp in length. Sfpq knockout (KO) mice showed progressive muscle mass reduction and metabolic myopathy characterized by glycogen accumulation and decreased abundance of mitochondrial oxidative phosphorylation complexes. Functional clustering analysis identified energy metabolism pathway genes as SFPQ's targets. These findings indicate target gene specificities and tissue-specific physiological functions of SFPQ in skeletal muscle.

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Loss of RNA-binding protein Sfpq causes long-gene transcriptopathy in skeletal muscle and severe muscle mass reduction with metabolic myopathy (skeletal muscle, mRNA-seq)

Project description:Growing evidences are suggesting that extra-long genes in mammals are vulnerable for full-gene length transcription and dysregulation of long genes is a mechanism underlying human genetic disorders. Skeletal muscle expresses Dystrophin which is 2.26 Mbp in length; however, how long-distance transcription is achieved is totally unknown. We had discovered RNA-binding protein SFPQ preferentially binds to long pre-mRNAs and specifically regulates the cluster of neuronal genes > 100 kbp. Here we investigated the roles of SFPQ for long gene expression, target specificities, and also physiological functions in skeletal muscle. Loss of Sfpq selectively downregulated genes >100 kbp including Dystrophin and caused progressive muscle mass reduction and metabolic myopathy characterized by glycogen accumulation and decreased abundance of mitochondrial oxidative phosphorylation complexes. Functional clustering analysis identified metabolic pathway related genes as the targets of SFPQ. These findings indicate target gene specificities and tissue-specific physiological functions of SFPQ in skeletal muscle.

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Loss of RNA-binding protein Sfpq causes long-gene transcriptopathy in skeletal muscle and severe muscle mass reduction with metabolic myopathy (Primary culture, mRNA-seq)

Project description:Growing evidences are suggesting that extra-long genes in mammals are vulnerable for full-gene length transcription and dysregulation of long genes is a mechanism underlying human genetic disorders. Skeletal muscle expresses Dystrophin which is 2.26 Mbp in length; however, how long-distance transcription is achieved is totally unknown. We had discovered RNA-binding protein SFPQ preferentially binds to long pre-mRNAs and specifically regulates the cluster of neuronal genes > 100 kbp. Here we investigated the roles of SFPQ for long gene expression, target specificities, and also physiological functions in skeletal muscle. Loss of Sfpq selectively downregulated genes >100 kbp including Dystrophin and caused progressive muscle mass reduction and metabolic myopathy characterized by glycogen accumulation and decreased abundance of mitochondrial oxidative phosphorylation complexes. Functional clustering analysis identified metabolic pathway related genes as the targets of SFPQ. These findings indicate target gene specificities and tissue-specific physiological functions of SFPQ in skeletal muscle.

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Loss of RNA-binding protein Sfpq causes long-gene transcriptopathy in skeletal muscle and severe muscle mass reduction with metabolic myopathy (Primary culture, rRNA depleted RNA-seq)

Project description:Growing evidences are suggesting that extra-long genes in mammals are vulnerable for full-gene length transcription and dysregulation of long genes is a mechanism underlying human genetic disorders. Skeletal muscle expresses Dystrophin which is 2.26 Mbp in length; however, how long-distance transcription is achieved is totally unknown. We had discovered RNA-binding protein SFPQ preferentially binds to long pre-mRNAs and specifically regulates the cluster of neuronal genes > 100 kbp. Here we investigated the roles of SFPQ for long gene expression, target specificities, and also physiological functions in skeletal muscle. Loss of Sfpq selectively downregulated genes >100 kbp including Dystrophin and caused progressive muscle mass reduction and metabolic myopathy characterized by glycogen accumulation and decreased abundance of mitochondrial oxidative phosphorylation complexes. Functional clustering analysis identified metabolic pathway related genes as the targets of SFPQ. These findings indicate target gene specificities and tissue-specific physiological functions of SFPQ in skeletal muscle.

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