细胞类型特定调节器RBPMS通过更高阶的寡合化和与其他拼接调节器的异型相互作用切换替代拼接
Yi Yang1, Giselle C Lee1, Erick Nakagaki-Silva1
1Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK.
Nucleic acids research
|August 7, 2023
概括
特定于光滑肌肉的RNA结合蛋白基因序列 (RBPMS) 通过防止拼接复杂组合来调节替代拼接. 这个过程涉及RBPMS内在无序区域 (IDR) 和与其他拼接因素的相互作用.
科学领域:
- 分子生物学分子生物学
- 在RNA生物学,RNA生物学.
- 基因法规 基因法规
背景情况:
- 替代性mRNA前拼接是由RNA结合蛋白 (RBPs) 控制的,这些蛋白质可以多价值地结合RNA.
- 广泛表达的RBPs调节剪接,但需要细胞特异性因素来引起细胞特异性效应.
- 本质上有障碍的区域 (IDR) 和多个RNA结合域有助于RBP多价值.
研究的目的:
- 研究细胞特异性调节器如何与构成性RBP在替代拼接中协作.
- 阐明RBPMS赋予光滑肌肉细胞特定替代拼接的机制.
主要方法:
- 在无细胞试验中使用重组RBPMS来研究Tpm1外子3的替代拼接.
- 研究了RBPMS的C端内在失序区域 (IDR) 的作用.
- 研究了RBPMS,MBNL1和RBFOX2.2之间的相互作用.
主要成果:
- 再组合的RBPMS单独在体外诱导了Tpm1外因子3的光滑肌细胞特异性替代拼接.
- RBPMS活动取决于其C端IDR,该IDR介导自我组装和RNA结合.
- RBPMS与MBNL1和RBFOX2.2合作组建了稳定的监管综合体.
结论:
- RBPMS通过防止依赖ATP的拼接复合体组合,起到光滑肌肉特异性调节者的作用.
- RBPMS的IDR对其功能至关重要,使其能够实现动态自组装和合作互动.
- RBPMS与广泛表达的拼接因子合作,以实现细胞特异的替代拼接调节.
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