MicroRNAs and the Regulation of Tau Metabolism.
MicroRNAs and the Regulation of Tau Metabolism.
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DOI：
10.1155/2012/406561
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发表时间：
2012
影响因子：
--
通讯作者：
Buée L
中科院分区：
文献类型：
--
作者：
Hébert SS;Sergeant N;Buée L
Tau磷酸化和/或选择性剪接的异常调节与一大组(>；20)神经退行性疾病的发展有关，统称为tauopathies，最常见的是阿尔茨海默病。尽管进行了大量的研究，但对参与内源性tau转录和转录后调控的分子机制知之甚少，尤其是在神经元中。最近，我们发现在前脑缺乏DICER的小鼠表现出进行性的神经变性，伴随着tau磷酸化和剪接的疾病样变化。DICER是microRNAs(MiRNAs)生物发生中的关键酶，microRNAs是作为RNA诱导沉默复合体(RISC)的一部分，在转录后水平抑制基因表达的非编码小RNA。我们确定miR-16和miR-132分别是神经元tau磷酸化和tau外显子10剪接的内源性调节剂。有趣的是，这些miRNAs与细胞存活和功能有关，而miR-16/132水平的变化与人类神经退行性疾病的tau病理相关。因此，了解miRNA网络如何影响tau代谢以及可能的其他生物系统，可能会为tau病的分子原因提供重要线索，特别是更常见但了解较少的零星形式。
Abnormal regulation of tau phosphorylation and/or alternative splicing is associated with the development of a large (>20) group of neurodegenerative disorders collectively known as tauopathies, the most common being Alzheimer's disease. Despite intensive research, little is known about the molecular mechanisms that participate in the transcriptional and posttranscriptional regulation of endogenous tau, especially in neurons. Recently, we showed that mice lacking Dicer in the forebrain displayed progressive neurodegeneration accompanied by disease-like changes in tau phosphorylation and splicing. Dicer is a key enzyme in the biogenesis of microRNAs (miRNAs), small noncoding RNAs that function as part of the RNA-induced silencing complex (RISC) to repress gene expression at the posttranscriptional level. We identified miR-16 and miR-132 as putative endogenous modulators of neuronal tau phosphorylation and tau exon 10 splicing, respectively. Interestingly, these miRNAs have been implicated in cell survival and function, whereas changes in miR-16/132 levels correlate with tau pathology in human neurodegenerative disorders. Thus, understanding how miRNA networks influence tau metabolism and possibly other biological systems might provide important clues into the molecular causes of tauopathies, particularly the more common but less understood sporadic forms.