无意义介导的mRNA衰变通过上变位蛋白1影响眼面心脏牙综合征中的过度活跃根形成
Ryoto Machida1, Takuya Ogawa1, Kyaw Min Soe1
1Department of Maxillofacial Orthognathics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan.
Journal of oral biosciences
|January 20, 2024
概括
在BCOR中引起眼面心脏牙 (OFCD) 综合征的突变会影响牙根的生长. UPF1蛋白与突变的BCOR结合,影响BCOR和BMP2基因表达,可能解释OFCD综合征的发展.
科学领域:
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
- 牙科医学 牙科医学
背景情况:
- 眼脸心脏牙综合征 (OFCD) 是一种罕见的X相关疾病,与BCOR基因突变有关.
- 这种综合征的特征是牙根扩大 (牙根延长).
- 无意义介导的mRNA衰变 (NMD) 涉及到OFCD的发病,但其机制尚不清楚.
研究的目的:
- 调查上变位蛋白1 (UPF1) 在OFCD综合征的发病过程中的作用.
- 了解将BCOR突变,NMD和牙根过度生长联系在一起的分子机制.
主要方法:
- 用RNA免疫沉来评估UPF1对突变BCOR的结合.
- 使用定量实时PCR分析BCOR转录水平和基因表达.
- 细胞模型包括具有特定BCOR突变的牙周带细胞和原发性人类牙周带纤维细胞.
主要成果:
- 发现UPF1与突变的BCOR.的第9个外显子结合.
- UPF1的淘汰导致BCOR转录的增加.
- 突变的BCOR过度表达影响了骨形态遗传蛋白2 (BMP2) 的表达.
结论:
- BCOR突变通过UPF1调节BCOR转录,可能会影响BMP2的表达.
- 由BCOR突变引发的无意义介导的mRNA衰变可能导致OFCD综合征表型,包括延长的牙根.
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