OBSCN undergoes extensive alternative splicing during human cardiac and skeletal muscle development
Abstract Background Highly expressed in skeletal muscles, the gene Obscurin (i.e. OBSCN) has 121 non-overlapping exons and codes for some of the largest known mRNAs in the human genome. Furthermore, it plays an essential role in muscle development and function. Mutations in OBSCN are associated with...
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| Format: | Article |
| Language: | English |
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BMC
2025-03-01
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| Series: | Skeletal Muscle |
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| Online Access: | https://doi.org/10.1186/s13395-025-00374-6 |
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| author | Ali Oghabian Per Harald Jonson Swethaa Natraj Gayathri Mridul Johari Ella Nippala David Gomez Andres Francina Munell Jessica Camacho Soriano Maria Angeles Sanchez Duran Juha Sinisalo Heli Tolppanen Johanna Tolva Peter Hackman Marco Savarese Bjarne Udd |
| author_facet | Ali Oghabian Per Harald Jonson Swethaa Natraj Gayathri Mridul Johari Ella Nippala David Gomez Andres Francina Munell Jessica Camacho Soriano Maria Angeles Sanchez Duran Juha Sinisalo Heli Tolppanen Johanna Tolva Peter Hackman Marco Savarese Bjarne Udd |
| author_sort | Ali Oghabian |
| collection | DOAJ |
| description | Abstract Background Highly expressed in skeletal muscles, the gene Obscurin (i.e. OBSCN) has 121 non-overlapping exons and codes for some of the largest known mRNAs in the human genome. Furthermore, it plays an essential role in muscle development and function. Mutations in OBSCN are associated with several hypertrophic cardiomyopathies and muscular disorders. OBSCN undergoes extensive and complex alternative splicing, which is the main reason that its splicing regulation associated with skeletal and cardiac muscle development has not previously been thoroughly studied. Methods We analyzed RNA-Seq data from skeletal and cardiac muscles extracted from 44 postnatal individuals and six fetuses. We applied the intron/exon level splicing analysis software IntEREst to study the splicing of OBSCN in the studied samples. The differential splicing analysis was adjusted for batch effects. Our comparisons revealed the splicing variations in OBSCN between the human skeletal and cardiac muscle, as well as between post-natal muscle (skeletal and cardiac) and the pre-natal equivalent muscle. Results We detected several splicing regulations located in the 5’end, 3’ end, and the middle of OBSCN that are associated with human cardiac or skeletal muscle development. Many of these alternative splicing events have not previously been reported. Our results also suggest that many of these muscle-development associated splicing events may be regulated by BUB3. Conclusions We conclude that the splicing of OBSCN is extensively regulated during the human skeletal/cardiac muscle development. We developed an interactive visualization tool that can be used by clinicians and researchers to study the inclusion of specific OBSCN exons in pre- and postnatal cardiac and skeletal muscles and access the statistics for the differential inclusion of the exons across the studied sample groups. The OBSCN exon inclusion map related to the human cardiac and skeletal muscle development is available at http://psivis.it.helsinki.fi:3838/OBSCN_PSIVIS/ . These findings are essential for an accurate pre- and postnatal clinical interpretation of the OBSCN exonic variants. |
| format | Article |
| id | doaj-art-bc4e47f6418c41c294603000be4973bb |
| institution | OA Journals |
| issn | 2044-5040 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Skeletal Muscle |
| spelling | doaj-art-bc4e47f6418c41c294603000be4973bb2025-08-20T02:17:10ZengBMCSkeletal Muscle2044-50402025-03-0115111310.1186/s13395-025-00374-6OBSCN undergoes extensive alternative splicing during human cardiac and skeletal muscle developmentAli Oghabian0Per Harald Jonson1Swethaa Natraj Gayathri2Mridul Johari3Ella Nippala4David Gomez Andres5Francina Munell6Jessica Camacho Soriano7Maria Angeles Sanchez Duran8Juha Sinisalo9Heli Tolppanen10Johanna Tolva11Peter Hackman12Marco Savarese13Bjarne Udd14Folkhälsan Research CenterFolkhälsan Research CenterFolkhälsan Research CenterFolkhälsan Research CenterFolkhälsan Research CenterPediatric Neuromuscular Unit. Child Neurology Department. Hospital Universitari Vall d’Hebron, Vall d’Hebron Research Institute (VHIR) ESPediatric Neuromuscular Unit. Child Neurology Department. Hospital Universitari Vall d’Hebron, Vall d’Hebron Research Institute (VHIR) ESHistology Department, Vall d’Hebron University Hospital ESPrenatal Diagnosis Department, Vall D’hebron University Hospital ESDepartment of Obstetrics, Maternal Fetal Medicine Unit, Universitat Autònoma de Barcelona, Hospital Vall D’hebronHelsinki University Central HospitalDepartment of Pathology, Transplantation Laboratory, University of HelsinkiFolkhälsan Research CenterFolkhälsan Research CenterFolkhälsan Research CenterAbstract Background Highly expressed in skeletal muscles, the gene Obscurin (i.e. OBSCN) has 121 non-overlapping exons and codes for some of the largest known mRNAs in the human genome. Furthermore, it plays an essential role in muscle development and function. Mutations in OBSCN are associated with several hypertrophic cardiomyopathies and muscular disorders. OBSCN undergoes extensive and complex alternative splicing, which is the main reason that its splicing regulation associated with skeletal and cardiac muscle development has not previously been thoroughly studied. Methods We analyzed RNA-Seq data from skeletal and cardiac muscles extracted from 44 postnatal individuals and six fetuses. We applied the intron/exon level splicing analysis software IntEREst to study the splicing of OBSCN in the studied samples. The differential splicing analysis was adjusted for batch effects. Our comparisons revealed the splicing variations in OBSCN between the human skeletal and cardiac muscle, as well as between post-natal muscle (skeletal and cardiac) and the pre-natal equivalent muscle. Results We detected several splicing regulations located in the 5’end, 3’ end, and the middle of OBSCN that are associated with human cardiac or skeletal muscle development. Many of these alternative splicing events have not previously been reported. Our results also suggest that many of these muscle-development associated splicing events may be regulated by BUB3. Conclusions We conclude that the splicing of OBSCN is extensively regulated during the human skeletal/cardiac muscle development. We developed an interactive visualization tool that can be used by clinicians and researchers to study the inclusion of specific OBSCN exons in pre- and postnatal cardiac and skeletal muscles and access the statistics for the differential inclusion of the exons across the studied sample groups. The OBSCN exon inclusion map related to the human cardiac and skeletal muscle development is available at http://psivis.it.helsinki.fi:3838/OBSCN_PSIVIS/ . These findings are essential for an accurate pre- and postnatal clinical interpretation of the OBSCN exonic variants.https://doi.org/10.1186/s13395-025-00374-6Neuromuscular diseasesOBSCN/RNA splicingExon inclusionMuscle development |
| spellingShingle | Ali Oghabian Per Harald Jonson Swethaa Natraj Gayathri Mridul Johari Ella Nippala David Gomez Andres Francina Munell Jessica Camacho Soriano Maria Angeles Sanchez Duran Juha Sinisalo Heli Tolppanen Johanna Tolva Peter Hackman Marco Savarese Bjarne Udd OBSCN undergoes extensive alternative splicing during human cardiac and skeletal muscle development Skeletal Muscle Neuromuscular diseases OBSCN/RNA splicing Exon inclusion Muscle development |
| title | OBSCN undergoes extensive alternative splicing during human cardiac and skeletal muscle development |
| title_full | OBSCN undergoes extensive alternative splicing during human cardiac and skeletal muscle development |
| title_fullStr | OBSCN undergoes extensive alternative splicing during human cardiac and skeletal muscle development |
| title_full_unstemmed | OBSCN undergoes extensive alternative splicing during human cardiac and skeletal muscle development |
| title_short | OBSCN undergoes extensive alternative splicing during human cardiac and skeletal muscle development |
| title_sort | obscn undergoes extensive alternative splicing during human cardiac and skeletal muscle development |
| topic | Neuromuscular diseases OBSCN/RNA splicing Exon inclusion Muscle development |
| url | https://doi.org/10.1186/s13395-025-00374-6 |
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