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嵌入大型拼接调节器序列组合中的深层内在RbFox图案集群调节替代拼接
Francesco Tomassoni-Ardori1, Mary Ellen Palko1, Melissa Galloux2
1Neural Development Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, 21702, USA.
bioRxiv : the preprint server for biology
|April 1, 2025
概括
由RbFox1蛋白调节的聚类RNA结合基因 (U) GCAUG,对于哺乳动物基因的替代拼接至关重要. 这些图案嵌入大型拼接调节器 (LASR) 结合序列组件中,控制基因异型表达.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 在RNA生物学,RNA生物学.
背景情况:
- RbFox RNA结合蛋白是哺乳动物发育和器官功能中替代拼接的关键调节者.
- RbFox蛋白与RNA基因结合,包括 (U) GCAUG,其亲和力和度依赖性各不相同.
- 广泛传播的RbFox动图在基因调节中的等级作用仍然不清楚.
研究的目的:
- 调查聚类RbFox图案在替代拼接调节中的作用.
- 确定RbFox图案集群如何影响基因异型表达.
- 阐明RbFox蛋白招募和复合形成与拼接调节器的机制.
主要方法:
- 在小鼠和人类基因中的 (U) GCAUG集群的生物信息分析.
- 综合分析eCLIP和RNAseq数据以识别Rbfox1相关的集群.
- 在细菌人工染色体中进行重组突变发生,以研究NTrk2基因拼接.
- 研究Rbfox1/LASR复合物的形成.
主要成果:
- 深度内在的,紧密集群的RbFox1基因被确定为替代性外子拼接的关键调节者.
- (U) GCAUG集群在哺乳动物基因中普遍存在,并嵌入绑定大拼接调节器组合 (LASR) 的序列中.
- 基因与Rbfox1 eCLIP-峰值在这些集群附近显示增加RNA异形调制;集群的动机是必要的RbFox1-介导的NTrk2拼接调节.
结论:
- 集群的内基RbFox结合基因,特别是 (U) GCAUG,对于哺乳动物替代拼接中的RbFox1功能至关重要.
- 这些图案与LASR结合序列合作,招募RbFox1蛋白质,形成一个功能拼接复合体.
- 这些发现突出了聚类内基基因作为RbFox1活动的关键决定因素和致病突变的潜在地点.
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