MicroRNA 26b encoded by the intron of small CTD phosphatase (SCP) 1 has an antagonistic effect on its host gene
MicroRNA 26b encoded by the intron of small CTD phosphatase (SCP) 1 has an antagonistic effect on its host gene
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DOI：
10.1002/jcb.24222
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发表时间：
2012-11-01
影响因子：
4
通讯作者：
Ono, Koh
中科院分区：
文献类型：
--
作者：
Sowa, Naoya;Horie, Takahiro;Ono, Koh
基因表达的组织特异性模式在每个器官的独特特征中起着重要作用。小CTD磷酸酶（SCP）13被阻遏元件1（RE-1）沉默转录因子/神经元限制性沉默因子（REST/NRSF）募集到含有RE-1元件的神经元基因，导致非神经元细胞中的神经元基因沉默。SCP在心脏中高度表达，并含有microRNA（miR）-26b，26 a-2和26 a-1，其内含子中具有相同的种子序列。因此，我们试图研究miR-26 b及其宿主基因在乳鼠心肌细胞中的作用。过表达miR-26 b可抑制心钠素、β-MHC和ACTA 1的mRNA表达水平，并减少心肌细胞的细胞表面积。我们证实miR-26 b靶向GATA 4的3'非翻译区（3' UTR）和经典瞬时受体电位通道（TRPC）3。相反，内源性miR-26 b家族的沉默增强了TRPC 3和GATA 4的表达水平。另一方面，SCP 1过表达诱导心钠素和β MHC的mRNA表达，并增加心肌细胞的细胞表面积。接下来，我们比较了SCP 1及其内含子和SCP 1 cDNA过表达的影响，以观察SCP 1表达对心肌肥厚的净功能。当SCP 1的表达水平相同时，SCP 1 cDNA的过表达比含内含子的SCP 1 cDNA具有更大的诱导心肌肥大的作用。总之，SCP 1本身具有诱导心脏肥大的潜力;然而，这种作用被心肌细胞中的内含子miR-26 b抑制。miR-26 b对其宿主基因SCP 1具有拮抗作用。J.细胞。113：34553465，2012. (C)2012 Wiley Periodicals，Inc.
Tissue-specific patterns of gene expression play an important role in the distinctive features of each organ. Small CTD phosphatases (SCPs) 13 are recruited by repressor element 1 (RE-1)-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells. SCPs are highly expressed in the heart and contain microRNAs (miR)-26b, 26a-2, and 26a-1 with the same seed sequence in their introns. Therefore, we tried to investigate the roles of miR-26b and its host gene in neonatal rat cardiomyocytes. Overexpression of miR-26b suppressed the mRNA expression levels of ANF, beta MHC, and ACTA1 and reduced the cell surface area in cardiomyocytes. We confirmed that miR-26b targets the 3' untranslated region (3'UTR) of GATA4 and canonical transient receptor potential channel (TRPC) 3. Conversely, silencing of the endogenous miR-26b family enhanced the expression levels of TRPC3 and GATA4. On the other hand, overexpression of SCP1 induced the mRNA expression of ANF and beta MHC and increased the cell surface area in cardiomyocytes. Next, we compared the effect of overexpression of SCP1 with its introns and SCP1 cDNA to observe the net function of SCP1 expression on cardiac hypertrophy. When the expression levels of SCP1 were the same, the overexpression of SCP1 cDNA had a greater effect at inducing cardiac hypertrophy than SCP1 cDNA with its intron. In conclusion, SCP1 itself has the potential to induce cardiac hypertrophy; however, the effect is suppressed by intronic miR-26b in cardiomyocytes. miR-26b has an antagonistic effect on its host gene SCP1. J. Cell. Biochem. 113: 34553465, 2012. (C) 2012 Wiley Periodicals, Inc.