Stimulation of StAR expression by cAMP is controlled by inhibition of highly inducible SIK1 via CRTC2, a co-activator of CREB.
Stimulation of StAR expression by cAMP is controlled by inhibition of highly inducible SIK1 via CRTC2, a co-activator of CREB.
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DOI：
10.1016/j.mce.2015.01.022
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发表时间：
2015-06-15
影响因子：
4.1
通讯作者：
Jefcoate, Colin
中科院分区：
文献类型：
--
作者：
Lee, Jinwoo;Tong, Tiegang;Takemori, Hiroshi;Jefcoate, Colin
在小鼠类固醇生成细胞中，胆固醇代谢的激活是由类固醇生成急性调节蛋白(STAR)介导的。在这里，我们看到了STAR转录、剪接和转录后处理的协调调控，这些调控是由盐诱导蛋白激酶(SIK1)和CREB调节的转录共激活因子(CRTC2)同步进行的。为了检测单细胞中的初级RNA(PRNA)、剪接初级RNA(Sp-RNA)和mRNA，我们利用荧光原位杂交(FISH)产生了探针集。这些方法使我们能够解决STAR基因表达的本质，并通过直接检测来可视化蛋白质与核酸的相互作用。我们发现SIK1通过抑制CRTC2介导的加工来抑制Y1肾上腺和MA10睾丸细胞中STAR的表达。数字图像分析与总细胞培养的qPCR分析相匹配。有证据表明，StAR PRNA和Sp-RNA在细胞核的基因位点上有空间分离的积累。这些发现表明，cAMP、SIK和CRTC通过激活单个STAR基因座来调节STAR的表达。
In mouse steroidogenic cells the activation of cholesterol metabolism is mediated by steroidogenic acute regulatory protein (StAR). Here, we visualized a coordinated regulation of StAR transcription, splicing and post-transcriptional processing, which are synchronized by salt inducible kinase (SIK1) and CREB-regulated transcription coactivator (CRTC2). To detect primary RNA (pRNA), spliced primary RNA (Sp-RNA) and mRNA in single cells, we generated probe sets by using fluorescence in situ hybridization (FISH). These methods allowed us to address the nature of StAR gene expression and to visualize protein–nucleic acid interactions through direct detection. We show that SIK1 represses StAR expression in Y1 adrenal and MA10 testis cells through inhibition of processing mediated by CRTC2. Digital image analysis matches qPCR analyses of the total cell culture. Evidence is presented for spatially separate accumulation of StAR pRNA and Sp-RNA at the gene loci in the nucleus. These findings establish that cAMP, SIK and CRTC mediate StAR expression through activation of individual StAR gene loci.
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DOI：
10.1038/nrm3072
发表时间：
2011-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.8
作者：
Liu, Ying;Poon, Victoria;Aguilera, Greti
通讯作者：
Aguilera, Greti
影响因子：
15.9
作者：
Jefcoate, C
通讯作者：
Jefcoate, C
影响因子：
--
作者：
Manna, PR;Dyson, MT;Stocco, DM
通讯作者：
Stocco, DM
影响因子：
3.5
作者：
Duan, Haichuan;Jefcoate, Colin R.
通讯作者：
Jefcoate, Colin R.