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在小鼠前脑和脊髓中μ-阿片类受体的转录变异

Magdalena Chrószcz¹, Jacek Hajto², Klaudia Misiołek¹

¹Department of Molecular Neuropharmacology, Maj Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland.

|August 26, 2024

概括

主要小鼠Oprm1转录有一个长3'未翻译区域,与基因组注释不同. 这一发现对于理解μ-阿片类受体 (Oprm1) 功能和开发向疗法至关重要.

科学领域:

神经科学是一个神经科学.
基因组学就是基因组学.
分子生物学分子生物学

背景情况:

Oprm1基因编码了μ-阿片类受体,对于疼痛调节和成至关重要.
Oprm1表现出转录变异性,特别是在其3'区域,其功能后果尚不清楚.
了解Oprm1转录多样性是开发具有改善临床特征的选择性阿片类配体的关键.

研究的目的:

为了全面调查小鼠中枢神经系统中的Oprm1转录变异.
解决注释小鼠基因组序列和观察到的Oprm1转录之间的差异.
描述主要的Oprm1转录及其3'未翻译区域.

主要方法:

长读RNA测序 (RNAseq) 的小鼠中枢神经系统.
空间和单细胞转录组学绘制Oprm1变异表达的地图.
为了验证转录本地化和丰度,RNAscope in situ杂交.

主要成果:

在GRCm38/mm10基因组注释和Oprm1.1的RNA-seq数据之间发现了显著的不匹配.
主要的Oprm1转录具有10.2 kb 3'的未翻译区域,位于最长的注释外型的下游.
长3' UTR变异的表达在多个大脑区域和脊髓中得到证实,而参考/替代转录被最小检测.

结论:

在小鼠中占主导地位的Oprm1转录具有很长的3'未翻译区域,与当前的基因组注释相反.
这种长变体与人类OPRM1初级转录相同,并编码了相同的C端氨基酸序列.
对Oprm1转录变异的准确表征对于推动μ-阿片类受体研究和治疗开发至关重要.

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