在长期暴露于酒精后,在海马体中改变RNA剪接中PCBP1的保留作用
Luana Carvalho1,2, Hu Chen3, Mark Maienschein-Cline3,4
1Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, 60612, USA. luana.martinsdecarvalho@vcuhealth.org.
Molecular psychiatry
|August 3, 2023
概括
长期暴露于乙醇会改变大鼠和人类海马中的RNA拼接. 聚C结合蛋白1 (PCBP1) 影响HAPLN2拼接,可能会影响酒精使用障碍 (AUD) 中的神经传导速度.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 长期暴露于乙醇与基因表达的变化有关.
- RNA拼接因子与神经系统疾病有关.
研究的目的:
- 在老鼠和人类酒精使用障碍 (AUD) 中,在乙醇戒断期间研究海马体的RNA拼接变化.
- 为了确定这些变化中涉及的特定基因和拼接因素.
主要方法:
- 在乙醇戒断期间,大鼠海马体的转录组分析 (RNA-Seq).
- 来自AUD受试者的死后人类海马体的分析.
- RNA免疫沉 (RIP) 用于评估蛋白质-RNA相互作用.
主要成果:
- 在老鼠和人类海马体中增加了拼接因子聚r(C) 结合蛋白1 (PCBP1) 的表达.
- 在HAPLN2基因中差异化的外显子结合使用,包括在外显子4中的新的3'拼接位.
- 在异常HAPLN2结合部位附近的PCBP1关联在老鼠和人类样本中得到证实.
结论:
- 在长期暴露于乙醇后,PCBP1在异常的HAPLN2拼接中起着保留的作用.
- 改变HAPLN2拼接可能导致蛋白质功能丧失,可能会影响AUD的海马功能.
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