Regulation of PP2Cm expression by miRNA-204/211 and miRNA-22 in mouse and human cells

Aim： The mitochondrial targeted 2C-type serine/threonine protein phosphatase （PP2Cm） is encoded by the gene PPMIK and is highly conserved among vertebrates. PP2Cm plays a critical role in branched-chain amino acid catabolism and regulates cell survival. Its expression is dynamically regulated by the...

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Bibliographic Details
Published in:Acta pharmacologica Sinica 2015-12, Vol.36 (12), p.1480-1486
Main Authors: Pan, Bang-fen, Gao, Chen, Ren, Shu-xun, Wang, Yi-bin, Sun, Hai-peng, Zhou, Mei-yi
Format: Article
Language:English
Subjects:
3' Untranslated Regions
Animals
Cell Line
Gene Expression Regulation
Humans
Mice
MicroRNAs - genetics
miRNAs
mRNA水平
Original
Phosphoprotein Phosphatases - genetics
Protein Phosphatase 2C
RNA, Messenger - genetics
人类
基因编码
基因表达调控
小鼠
结合位点
节细胞
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Summary:Aim： The mitochondrial targeted 2C-type serine/threonine protein phosphatase （PP2Cm） is encoded by the gene PPMIK and is highly conserved among vertebrates. PP2Cm plays a critical role in branched-chain amino acid catabolism and regulates cell survival. Its expression is dynamically regulated by the nutrient environment and pathological stresses. However, little is known about the molecular mechanism underlying the regulation of PPMIK gene expression. In this study, we aimed to reveal how PPMIK expression is affected by miRNA-mediated post-transcriptional regulation. Methods： Computational analysis based on conserved miRNA binding motifs was applied to predict the candidate miRNAs that potentially affect PPMIK expression. Dual-luciferase reporter assay was performed to verify the miRNAs＇ binding sites in the PPMIK gene and their influence on PPM1K 3＇UTR activity. We further over-expressed the mimics of these miRNAs in human and mouse cells to examine whether miRNAs affected the mRNA level of PPMIK. Results： Computational analysis identified numerous miRNAs potentially targeting PPM1K. Luciferase reporter assays demonstrated that the 3＇UTR of PPMIK gene contained the recognition sites of miR-204 and miR-211. Overexpression of these miRNAs in human and mouse cells diminished the 3＇UTR activity and the endogenous mRNA level of PPMIK. However, the miR-22 binding site was found only in human and not mouse PPMIK 3＇UTR. Accordingly, PPMIK 3＇UTR activity was suppressed by miR-22 overexpression in human but not mouse cells. Conclusion： These data suggest that different miRNAs contribute to the regulation of PP2Cm expression in a species-specific manner. miR-204 and miR-211 are efficient in both mouse and human cells, while miR-22 regulates PP2Cm expression only in human cells.
ISSN:1671-4083
1745-7254
DOI:10.1038/aps.2015.119