rna结合蛋白HuR通过增加Drosha表达来调节microRNA的生物发生。

IF 3.5 3区 生物学 Q3 CELL BIOLOGY
Lin Liu , Linxiao Wang , Yanjun Wang , Ran Zhuang , Yuan Zhang , Junjie Li , Jiangang Xie , Wen Yin
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引用次数: 0

摘要

背景:microRNAs (miRNAs)的生物发生在各种应激源的反应中发生了实质性的变化。Drosha是miRNA生物发生的关键调节因子,在细胞对外部刺激的反应中起关键作用。rna结合蛋白hurr在细胞应激下上调。然而,在严重或长时间的应激条件下,HuR水平可能下降,损害其保护功能。方法:为了研究HuR对miRNA表达的影响,采用miRNA测序方法分析HuR沉默后IEC-6肠上皮细胞的表达情况。此外,我们还评估了HuR过表达对Drosha表达和活性的影响。生物信息学分析、生化分析和分子生物学技术被用来阐明HuR与Drosha mRNA相互作用的机制,调节其翻译和转录。结果:HuR沉默导致几乎所有mirna的显著下调,但未观察到对piRNA生物发生的影响。相反,HuR过表达导致Drosha表达增加,这是通过HuR直接结合Drosha mRNA的3'-UTR来调节的。此外,HuR通过提高c-Myc水平间接促进了Drosha转录。在胸部创伤小鼠模型中,肠上皮HuR表达减少与Drosha水平降低相关,损害miRNA的生物发生并增强细胞凋亡。结论:这些发现强调了HuR在通过Drosha调控miRNA生物发生中的重要作用,对应激反应和肠道损伤具有重要意义。HuR-Drosha轴成为调控miRNA生物发生的有希望的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The RNA-binding protein HuR regulates microRNA biogenesis via increased drosha expression

The RNA-binding protein HuR regulates microRNA biogenesis via increased drosha expression

Background

The biogenesis of microRNAs (miRNAs) undergoes substantial alterations in response to various stressors. Drosha, a pivotal regulator of miRNA biogenesis, plays a critical role in cellular responses to external stimuli. The RNA-binding protein HuR is upregulated upon cellular stress. However, under severe or prolonged stress conditions, HuR levels may decline, impairing its protective functions.

Methods

To investigate the influence of HuR on miRNA expression, miRNA sequencing was employed to profile expression in IEC-6 intestinal epithelial cells following HuR silencing. Additionally, the effect of HuR overexpression on Drosha expression and activity was assessed. Bioinformatics analyses, biochemical assays, and molecular biology techniques were utilized to elucidate the mechanisms by which HuR interacts with Drosha mRNA, modulating both its translation and transcription.

Results

HuR silencing resulted in a significant downregulation of nearly all miRNAs, with no observed impact on piRNA biogenesis. Conversely, HuR overexpression led to increased Drosha expression, regulated through HuR's direct binding to the 3′-UTR of Drosha mRNA. Moreover, HuR indirectly promoted Drosha transcription by elevating c-Myc levels. In a mouse model of thoracic trauma, diminished HuR expression in the intestinal epithelium correlated with reduced Drosha levels, impairing miRNA biogenesis and enhancing apoptosis.

Conclusions

These findings underscore the essential role of HuR in the regulation of miRNA biogenesis through Drosha, with implications for stress responses and intestinal injury. The HuR-Drosha axis emerges as a promising therapeutic target for modulating miRNA biogenesis.
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来源期刊
Experimental cell research
Experimental cell research 医学-细胞生物学
CiteScore
7.20
自引率
0.00%
发文量
295
审稿时长
30 days
期刊介绍: Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.
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