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首页> 外文期刊>BMC Molecular Biology >The 3' untranslated region of human Cyclin-Dependent Kinase 5 Regulatory subunit 1 contains regulatory elements affecting transcript stability
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The 3' untranslated region of human Cyclin-Dependent Kinase 5 Regulatory subunit 1 contains regulatory elements affecting transcript stability

机译：人类细胞周期蛋白依赖性激酶5调节亚基1的3'非翻译区包含影响转录物稳定性的调节元件

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Background CDK5R1 plays a central role in neuronal migration and differentiation during central nervous system development. CDK5R1 has been implicated in neurodegenerative disorders and proposed as a candidate gene for mental retardation. The remarkable size of CDK5R1 3'-untranslated region (3'-UTR) suggests a role in post-transcriptional regulation of CDK5R1 expression. Results The bioinformatic study shows a high conservation degree in mammals and predicts several AU-Rich Elements (AREs). The insertion of CDK5R1 3'-UTR into luciferase 3'-UTR causes a decreased luciferase activity in four transfected cell lines. We identified 3'-UTR subregions which tend to reduce the reporter gene expression, sometimes in a cell line-dependent manner. In most cases the quantitative analysis of luciferase mRNA suggests that CDK5R1 3'-UTR affects mRNA stability. A region, leading to a very strong mRNA destabilization, showed a significantly low half-life, indicating an accelerated mRNA degradation. The 3' end of the transcript, containing a class I ARE, specifically displays a stabilizing effect in neuroblastoma cell lines. We also observed the interaction of the stabilizing neuronal RNA-binding proteins ELAV with the CDK5R1 transcript in SH-SY5Y cells and identified three 3'-UTR sub-regions showing affinity for ELAV proteins. Conclusion Our findings evince the presence of both destabilizing and stabilizing regulatory elements in CDK5R1 3'-UTR and support the hypothesis that CDK5R1 gene expression is post-transcriptionally controlled in neurons by ELAV-mediated mechanisms. This is the first evidence of the involvement of 3'-UTR in the modulation of CDK5R1 expression. The fine tuning of CDK5R1 expression by 3'-UTR may have a role in central nervous system development and functioning, with potential implications in neurodegenerative and cognitive disorders.
机译：背景CDK5R1在中枢神经系统发育过程中的神经元迁移和分化中起着核心作用。 CDK5R1与神经退行性疾病有关，并被提议作为智力低下的候选基因。 CDK5R1 3'非翻译区（3'-UTR）的显着大小表明在CDK5R1表达的转录后调控中起作用。结果该生物信息学研究显示了对哺乳动物的高度保存，并预测了几种富含AU的元素（ARE）。将CDK5R1 3'-UTR插入荧光素酶3'-UTR会导致四种转染的细胞系中荧光素酶活性降低。我们鉴定了3'-UTR子区域，这些区域有时会以依赖细胞系的方式降低报告基因的表达。在大多数情况下，荧光素酶mRNA的定量分析表明CDK5R1 3'-UTR影响mRNA的稳定性。导致非常强烈的mRNA失稳的区域显示出明显较低的半衰期，表明mRNA降解加速。包含I ARE类的转录本的3'末端在神经母细胞瘤细胞系中特别显示出稳定作用。我们还观察到了稳定神经元RNA结合蛋白ELAV与SH-SY5Y细胞中CDK5R1转录物的相互作用，并鉴定了三个对ELAV蛋白具有亲和力的3'-UTR子区域。结论我们的发现表明CDK5R1 3'-UTR中既存在稳定又存在稳定的调控元件，并支持CDK5R1基因表达受ELAV介导的机制在神经元中转录后控制的假说。这是3'-UTR参与CDK5R1表达调节的第一个证据。 3'-UTR对CDK5R1表达的微调可能在中枢神经系统的发育和功能中起作用，对神经退行性和认知障碍具有潜在的影响。

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