OBSCN undergoes extensive alternative splicing throughout human cardiac and skeletal muscle development

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 human genome. Furthermore, it is known to play an essential role in muscle development and function. Mutations within OBSCN are known to cause several hypertrophic cardiomyopathies and muscular disorders. Even though OBSCN undergoes extensive alternative splicing, its splicing regulation associated with skeletal and cardiac muscle development has not previously been thoroughly studied. We study splicing of OBSCN in skeletal and cardiac muscles extracted from 41 postnatal individuals and 6 fetuses. We detect several splicing regulations located in 5’end, 3’ end, as well as in the middle of OBSCN. Many of these alternative splicing events have not previously been reported. These findings are essential for an accurate pre- and postnatal diagnosis and prognosis of OBSCN exonic variants. The muscle development OBSCN exon inclusion map is available at https://gacatag.shinyapps.io/OBSCN_PSIVIS/ . Fetal skeletal muscles (n=20) and fetal heart muscles (n=2), without muscle pathology, was obtained from voluntary termination of pregnancy (TOP). Furthermore, sample biopsies from an internal cohort of 41 individuals was collected. From the 2 fetuses (denoted with F1 and F2) various different muscle samples have been extracted. ------------------------------------- Authors state 'Raw data is not availalbe due to GDPR. For any further enquiries regarding the studied samples please contact [e-mail]".

基因Obscurin（即OBSCN）在骨骼肌中呈高表达，其含有121个不重叠外显子，编码人类基因组中已知的部分最大型mRNA分子。
此外，该基因在肌肉发育与功能维持中发挥关键作用。OBSCN基因突变可引发多种肥厚型心肌病及肌肉疾病。
尽管OBSCN存在广泛的可变剪接现象，但此前尚未有研究对其与骨骼肌、心肌发育相关的剪接调控机制进行系统深入的解析。
本研究针对41名产后个体及6名胎儿的骨骼肌与心肌组织，开展OBSCN剪接模式分析。
研究团队在OBSCN的5'端、3'端及中间区域均检测到多种剪接调控事件，其中多数可变剪接事件此前未见报道。
上述研究结果对于OBSCN外显子变异的精准产前、产后诊断及预后评估具有重要意义。
与肌肉发育相关的OBSCN外显子包含率图谱可通过以下链接获取：https://gacatag.shinyapps.io/OBSCN_PSIVIS/。
本研究的胎儿骨骼肌样本（n=20）及胎儿心肌样本（n=2）均来自无肌肉病理表现的自愿终止妊娠（Termination of Pregnancy，即TOP）受试者。
此外，本研究还收集了来自内部队列的41名个体的肌肉活检样本。
针对编号为F1和F2的2名胎儿，研究人员还获取了多种不同的肌肉样本。
研究团队声明：受通用数据保护条例（General Data Protection Regulation，即GDPR）限制，原始数据暂不对外公开。若需进一步咨询研究样本相关事宜，请联系[e-mail]。