Expression of Quaking RNA-Binding Protein in the Adult and Developing Mouse Retina.
Expression of Quaking RNA-Binding Protein in the Adult and Developing Mouse Retina.
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成年和发育中小鼠视网膜中颤动 RNA 结合蛋白的表达。
DOI：
10.1371/journal.pone.0156033
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Koike C
中科院分区：
文献类型：
--
作者：
Suiko T;Kobayashi K;Aono K;Kawashima T;Inoue K;Ku L;Feng Y;Koike C
Quaking (QKI) 属于含 KH 结构域的 RNA 结合蛋白 STAR 家族，在前 mRNA 剪接、microRNA 调节和环状 RNA 的形成中发挥作用。 QKI 在中枢和周围神经系统的髓磷脂生成中发挥着关键作用，并且与大脑中神经元-胶质细胞的命运决定有关；然而，QKI 在神经视网膜中的表达和功能尚不清楚。在这里，我们报告了 QKI RNA 结合蛋白在发育和成熟小鼠视网膜中的表达。 QKI 在发育中和成年视网膜中由 Müller 胶质细胞强烈表达。有趣的是，在发育过程中，QKI 在早期分化的神经元（例如水平细胞和无长突细胞）中表达，随后在后来分化的双极细胞中表达，但在光感受器中不表达。成人的神经元表达均较弱。在 QKI 亚型（5、6 和 7）中，QKI-5 是成人视网膜中主要表达的亚型。为了研究 QKI 在小鼠视网膜中的功能，我们检查了 quakingviable (qkv) 小鼠，该小鼠具有因 QKI 表达缺陷和成熟少突胶质细胞数量减少而导致的髓鞘形成障碍表型。在纯合 qkv 突变小鼠 (qkv/qkv) 中，QKI-6 和 7 的视神经表达水平降低，但 QKI-5 没有降低。在突变纯合子的视网膜中，QKI-5水平没有变化，而本来就很低的QKI-6和7水平也没有受到影响。我们得出结论，QKI 在发育中和成年的米勒神经胶质细胞中表达。 QKI 在视网膜发育过程中还在祖细胞和分化神经元中表达，但在成熟过程中表达减弱或减少。在 QKI 亚型中，我们发现 QKI-5 在成年小鼠视网膜中占主导地位。由于穆勒胶质细胞被认为与视网膜祖细胞具有相同的特性，因此我们的数据表明 QKI 可能有助于在分化为神经元之前维持视网膜祖细胞。另一方面，QKI 在不同视网膜神经元中的表达可能表明 QKI 在神经元细胞类型特异性命运决定和成熟中发挥作用。这些数据提出了 QKI 可能在神经胶质细胞和神经元的视网膜细胞命运决定和成熟中发挥作用的可能性。
Quaking (QKI), which belongs to the STAR family of KH domain-containing RNA-binding proteins, functions in pre-mRNA splicing, microRNA regulation, and formation of circular RNA. QKI plays critical roles in myelinogenesis in the central and peripheral nervous systems and has been implicated neuron-glia fate decision in the brain; however, neither the expression nor function of QKI in the neural retina is known. Here we report the expression of QKI RNA-binding protein in the developing and mature mouse retina. QKI was strongly expressed by Müller glial cells in both the developing and adult retina. Intriguingly, during development, QKI was expressed in early differentiating neurons, such as the horizontal and amacrine cells, and subsequently in later differentiating bipolar cells, but not in photoreceptors. Neuronal expression was uniformly weak in the adult. Among QKI isoforms (5, 6, and 7), QKI-5 was the predominantly expressed isoform in the adult retina. To study the function of QKI in the mouse retina, we examined quakingviable(qkv) mice, which have a dysmyelination phenotype that results from deficiency of QKI expression and reduced numbers of mature oligodendrocytes. In homozygous qkv mutant mice (qkv/qkv), the optic nerve expression levels of QKI-6 and 7, but not QKI-5 were reduced. In the retina of the mutant homozygote, QKI-5 levels were unchanged, and QKI-6 and 7 levels, already low, were also unaffected. We conclude that QKI is expressed in developing and adult Müller glia. QKI is additionally expressed in progenitors and in differentiating neurons during retinal development, but expression weakened or diminished during maturation. Among QKI isoforms, we found that QKI-5 predominated in the adult mouse retina. Since Müller glial cells are thought to share properties with retinal progenitor cells, our data suggest that QKI may contribute to maintaining retinal progenitors prior to differentiation into neurons. On the other hand, the expression of QKI in different retinal neurons may suggest a role in neuronal cell type specific fate determination and maturation. The data raises the possibility that QKI may function in retinal cell fate determination and maturation in both glia and neurons.