Identification of a microRNA that activates gene expression by repressing nonsense-mediated RNA decay.
Identification of a microRNA that activates gene expression by repressing nonsense-mediated RNA decay.
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DOI：
10.1016/j.molcel.2011.04.018
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发表时间：
2011-05-20
期刊：
影响因子：
16
通讯作者：
Wilkinson MF
中科院分区：
文献类型：
--
作者：
Bruno IG;Karam R;Huang L;Bhardwaj A;Lou CH;Shum EY;Song HW;Corbett MA;Gifford WD;Gecz J;Pfaff SL;Wilkinson MF
无义介导的衰变（NMD）在特定情况下降解含有终止密码子的正常和异常转录本。扰乱NMD的突变会导致人类神经系统疾病，这表明NMD在大脑中发挥作用。在这里，我们确定了一个脑特异性microRNA-miR-128-抑制NMD，从而控制神经细胞中的转录电池。miR-128通过靶向RNA解旋酶UPF 1和外显子连接复合物核心组分MLN 51来抑制NMD。miR-128调节NMD的能力是青蛙、鸡和哺乳动物中发生的保守反应。miR-128水平在分化的神经元细胞中和脑发育期间显著增加，导致NMD被抑制和通常被NMD靶向衰变的mRNA的上调;过度表达的是那些编码控制神经元发育和功能的蛋白质的mRNA。总之，这些结果表明存在一个保守的RNA电路连接microRNA和NMD途径，在发育过程中诱导细胞类型特异性转录。
Nonsense-mediated decay (NMD) degrades both normal and aberrant transcripts harboring stop codons in particular contexts. Mutations that perturb NMD cause neurological disorders in humans, suggesting that NMD has roles in the brain. Here, we identify a brain-specific microRNA—miR-128—that represses NMD and thereby controls batteries of transcripts in neural cells. miR-128 represses NMD by targeting the RNA helicase UPF1 and the exon-junction complex core component MLN51. The ability of miR-128 to regulate NMD is a conserved response occuring in frogs, chickens, and mammals. miR-128 levels are dramatically increased in differentiating neuronal cells and during brain development, leading to repressed NMD and upregulation of mRNAs normally targeted for decay by NMD; overrepresented are those encoding proteins controlling neuron development and function. Together, these results suggest the existence of a conserved RNA circuit linking the microRNA and NMD pathways that induces cell type-specific transcripts during development.
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影响因子：
64.5
作者：
Hogg JR;Goff SP
通讯作者：
Goff SP
miRNAMAP：哺乳动物基因组中microRNA基因及其靶基因的基因组图。
影响因子：
14.9
作者：
Hsu, Paul W. C.;Huang, Hsien-Da;Hsu, Sheng-Da;Lin, Li-Zen;Tsou, Ann-Ping;Tseng, Ching-Ping;Stadler, Peter F.;Washietl, Stefan;Hofacker, Ivo L.
通讯作者：
Hofacker, Ivo L.
影响因子：
56.9
作者：
Kim, Jongpil;Inoue, Keiichi;Abeliovich, Asa
通讯作者：
Abeliovich, Asa
影响因子：
64.5
作者：
Giorgi, Corinna;Yeo, Gene W.;Moore, Melissa J.
通讯作者：
Moore, Melissa J.
影响因子：
30.8
作者：
Mendell, JT;Sharifi, NA;Dietz, HC
通讯作者：
Dietz, HC