The QKI-6 RNA binding protein regulates actin-interacting protein-1 mRNA stability during oligodendrocyte differentiation.
The QKI-6 RNA binding protein regulates actin-interacting protein-1 mRNA stability during oligodendrocyte differentiation.
复制标题
DOI：
10.1091/mbc.e10-04-0305
复制
发表时间：
2010-09-01
影响因子：
3.3
通讯作者：
Richard S
中科院分区：
文献类型：
--
作者：
Doukhanine E;Gavino C;Haines JD;Almazan G;Richard S
我们使用无偏方法确定QKI-6 RNA结合蛋白的新mRNA靶标。我们发现AIP-1 mRNA在其3 ' -UTR内被QKI-6结合。这种调节在少突胶质细胞中观察到，它对少突胶质细胞的生长至关重要。震颤活鼠（qkv）是一种髓鞘发育异常的动物模型。在中枢神经系统髓鞘形成过程中，少突胶质细胞（OLs）中QKI-6和QKI-7细胞质亚型的表达缺失导致了qkv小鼠表型。已知QKI RNA结合蛋白调节OLs中细胞周期蛋白和髓鞘成分的RNA代谢；然而，在OL成熟和分化过程中，它们在重组细胞骨架或过程生长中的作用知之甚少。在这里，我们通过二维差分凝胶电泳鉴定了肌动蛋白相互作用蛋白(AIP)-1 mRNA是QKI-6的靶标。AIP-1 mRNA在其3 ' -非翻译区含有一个一致的QKI应答元件，当与QKI-6结合时，会降低AIP-1 mRNA的半衰期。虽然已知QKI-6的表达在OL分化和中枢神经鞘形成过程中增加，但我们发现这种增加与大鼠脑中AIP-1表达的相应减少是平行的。此外，在其ol中缺乏QKI-6和QKI-7的qkv/qkv小鼠ol中AIP-1水平升高。此外，含有AIP-1小干扰RNA的原代大鼠OL前体在OL过程中表现出缺陷。我们的研究结果表明，QKI rna结合蛋白通过调节AIP-1的表达来调节OL的分化。
We identify new mRNA targets for the QKI-6 RNA binding proteins using an unbiased approach. We show that AIP-1 mRNA is bound by QKI-6 within its 3′-UTR. This regulation is observed in oligodendrocytes and it is essential for oligodendrocyte process outgrowth. The quaking viable (qkv) mice represent an animal model of dysmyelination. The absence of expression of the QKI-6 and QKI-7 cytoplasmic isoforms in oligodendrocytes (OLs) during CNS myelination causes the qkv mouse phenotype. The QKI RNA-binding proteins are known to regulate RNA metabolism of cell cycle proteins and myelin components in OLs; however, little is known of their role in reorganizing the cytoskeleton or process outgrowth during OL maturation and differentiation. Here, we identify the actin-interacting protein (AIP)-1 mRNA as a target of QKI-6 by using two-dimensional differential gel electrophoresis. The AIP-1 mRNA contains a consensus QKI response element within its 3′-untranslated region that, when bound by QKI-6, decreases the half-life of the AIP-1 mRNA. Although the expression of QKI-6 is known to increase during OL differentiation and CNS myelination, we show that this increase is paralleled with a corresponding decrease in AIP-1 expression in rat brains. Furthermore, qkv/qkv mice that lack QKI-6 and QKI-7 within its OLs had an increased level of AIP-1 in OLs. Moreover, primary rat OL precursors harboring an AIP-1 small interfering RNA display defects in OL process outgrowth. Our findings suggest that the QKI RNA-binding proteins regulate OL differentiation by modulating the expression of AIP-1.