hnRNPA1 autoregulates its own mRNA expression to remain non-cytotoxic

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• 作者：Hiroaki Suzuki ; Masaaki Matsuoka
• 关键词：hnRNPA1 ; Autoregulation ; Splicing ; Cell death
• 刊名：Molecular and Cellular Biochemistry
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：427
• 期：1-2
• 页码：123-131
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biochemistry, general; Medical Biochemistry; Oncology; Cardiology;
• 出版者：Springer US
• ISSN：1573-4919
• 卷排序：427

文摘

Heterogeneous nuclear ribonucleoprotein (hnRNP)A1, a member of the hnRNP family, is involved in a variety of RNA metabolisms. The hnRNPA1 expression is altered in some human diseases and mutations of the hnRNPA1 gene cause amyotrophic lateral sclerosis and multisystem proteinopathy. It has been therefore assumed that the dysregulation of hnRNPA1 is linked to the pathogenesis of the diseases. However, the mechanism underlying the regulation of the hnRNPA1 expression remains unknown. In this study, using cell-based models, we have found that hnRNPA1 negatively regulates its own mRNA expression by inhibiting the intron10 splicing of hnRNPA1 pre-mRNA. This mechanism likely serves as an autoregulation of the hnRNPA1 expression. We have also found that a low-grade excess of hnRNPA1 expression causes cytotoxicity by activating the mitochondrial apoptosis pathway. Collectively, these data suggest that the level of hnRNPA1 is strictly controlled to be within a certain range by the mRNA autoregulation in the physiological condition so that the cytotoxicity-causative alteration of hnRNPA1 expression does not take place.