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Novel alternatively-spliced exons of the VRK2 gene in mouse brain and microglial cells.
Molecular Biology Reports ( IF 2.6 ) Pub Date : 2020-06-24 , DOI: 10.1007/s11033-020-05584-3
Salsabil Almarzooq 1 , Jaedeok Kwon 1 , Ashleigh Willis 1 , John Craig 1 , Brian J Morris 1
Affiliation  

Common sequence variations in the VRK2 gene contribute to genetic risk for various psychiatric diseases including schizophrenia and major depressive disorder. Despite the clear importance of studying the regulation and function of VRK2 for understanding the causes of these diseases, the organisation and expression of the gene remain poorly characterised. Using reverse-transcriptase-PCR, we have amplifed exons of Vrk2 mRNA from regions of mouse brain, and from different cell classes comprising neurones, astrocytes and microglial cells. We find that Vrk2 mRNA is expressed in all cell types, and that the splicing of the mouse Vrk2 gene is much more complex than previously appreciated. In addition to the predicted alternative splicing (absence/presence) of the penultimate 3 prime exon, we also detected a variety of 5 prime structures, including two novel exons spanning the first characterised exon (exon 1), which we term exons 1a and 1b. While expressed in neurones and astrocytes, exon 1b was not expressed in microglial cells. Expression of transcripts containing exon 1a in microglia was increased by immune stimulation. An additional truncated transcript lacking 7 central exons was also identified. As with the human gene, the results confirm complex patterns of alternative splicing which are likely to be relevant for understanding the physiological and pathological function of the gene in the CNS.



中文翻译:

小鼠大脑和小胶质细胞中VRK2基因的新型剪接外显子。

VRK2基因的常见序列变异会导致多种精神疾病(包括精神分裂症和重度抑郁症)的遗传风险。尽管研究VRK2的调节和功能对于理解这些疾病的病因具有明显的重要性,但该基因的组织和表达仍然缺乏良好的表征。使用逆转录酶-PCR,我们已经扩增了小鼠大脑区域以及包括神经元,星形胶质细胞和小胶质细胞在内的不同细胞类别的Vrk2 mRNA的外显子。我们发现Vrk2 mRNA在所有细胞类型中都有表达,并且小鼠Vrk2的剪接基因比以前认为的复杂得多。除了倒数第二个3个主要外显子的预测的可变剪接(不存在),我们还检测了5种主要结构,包括跨越第一个特征性外显子(外显子1)的两个新外显子,我们将其称为外显子1a和1b。 。虽然在神经元和星形胶质细胞中表达,外显子1b在小胶质细胞中不表达。免疫刺激增加了小胶质细胞中含有外显子1a的转录物的表达。还确定了另外一个缺少7个中央外显子的截短转录本。与人类基因一样,结果证实了可变剪接的复杂模式,这可能与理解基因在中枢神经系统中的生理和病理功能有关。

更新日期:2020-06-25
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