在人类心脏和骨骼肌发育过程中，obcn经历了广泛的选择性剪接。

IF 5.3 2区医学 Q2 CELL BIOLOGY

Skeletal Muscle Pub Date : 2025-03-01 DOI:10.1186/s13395-025-00374-6

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

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引用次数: 0

摘要

背景：在骨骼肌中高度表达的基因Obscurin（即obcn）有121个不重叠的外显子，并编码人类基因组中一些已知的最大mrna。此外，它在肌肉发育和功能中起着至关重要的作用。obn突变与几种肥厚性心肌病和肌肉疾病有关。obn经历了广泛而复杂的选择性剪接，这是其与骨骼和心肌发育相关的剪接调控尚未被深入研究的主要原因。方法：我们分析了44例产后个体和6例胎儿的骨骼肌和心肌的RNA-Seq数据。我们应用内含子/外显子水平剪接分析软件IntEREst对所研究样本中的obn剪接进行了研究。对差异剪接分析进行了批次效应调整。我们的比较揭示了人类骨骼肌和心肌之间，以及出生后肌肉（骨骼和心脏）和产前等效肌肉之间的obn剪接变化。结果：我们检测到位于bln的5‘端、3’端和中间的几个剪接调控与人类心脏或骨骼肌的发育有关。许多这些选择性剪接事件以前没有报道过。我们的研究结果还表明，许多与肌肉发育相关的剪接事件可能受到BUB3的调节。结论：我们得出结论，在人类骨骼肌/心肌发育过程中，obn的剪接受到广泛调节。我们开发了一种交互式可视化工具，临床医生和研究人员可以使用它来研究产前和产后心脏和骨骼肌中特定的obn外显子的包含情况，并获得在所研究样本组中外显子差异包含的统计数据。与人类心脏和骨骼肌发育相关的obn外显子包含图谱可在http://psivis.it.helsinki.fi:3838/OBSCN_PSIVIS/上获得。这些发现对于准确的产前和产后临床解释obn外显子变异至关重要。

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OBSCN undergoes extensive alternative splicing during human cardiac and skeletal muscle development.

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.

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来源期刊

Skeletal Muscle CELL BIOLOGY-

CiteScore

9.10

自引率

0.00%

发文量

审稿时长

12 weeks

期刊介绍： The only open access journal in its field, Skeletal Muscle publishes novel, cutting-edge research and technological advancements that investigate the molecular mechanisms underlying the biology of skeletal muscle. Reflecting the breadth of research in this area, the journal welcomes manuscripts about the development, metabolism, the regulation of mass and function, aging, degeneration, dystrophy and regeneration of skeletal muscle, with an emphasis on understanding adult skeletal muscle, its maintenance, and its interactions with non-muscle cell types and regulatory modulators. Main areas of interest include: -differentiation of skeletal muscle- atrophy and hypertrophy of skeletal muscle- aging of skeletal muscle- regeneration and degeneration of skeletal muscle- biology of satellite and satellite-like cells- dystrophic degeneration of skeletal muscle- energy and glucose homeostasis in skeletal muscle- non-dystrophic genetic diseases of skeletal muscle, such as Spinal Muscular Atrophy and myopathies- maintenance of neuromuscular junctions- roles of ryanodine receptors and calcium signaling in skeletal muscle- roles of nuclear receptors in skeletal muscle- roles of GPCRs and GPCR signaling in skeletal muscle- other relevant aspects of skeletal muscle biology. In addition, articles on translational clinical studies that address molecular and cellular mechanisms of skeletal muscle will be published. Case reports are also encouraged for submission. Skeletal Muscle reflects the breadth of research on skeletal muscle and bridges gaps between diverse areas of science for example cardiac cell biology and neurobiology, which share common features with respect to cell differentiation, excitatory membranes, cell-cell communication, and maintenance. Suitable articles are model and mechanism-driven, and apply statistical principles where appropriate; purely descriptive studies are of lesser interest.