An RNA-binding protein, Qki5, regulates embryonic neural stem cells through pre-mRNA processing in cell adhesion signaling.
An RNA-binding protein, Qki5, regulates embryonic neural stem cells through pre-mRNA processing in cell adhesion signaling.
复制标题
DOI：
10.1101/gad.300822.117
复制
发表时间：
2017-09-15
影响因子：
10.5
通讯作者：
Yano M
中科院分区：
文献类型：
--
作者：
Hayakawa-Yano Y;Suyama S;Nogami M;Yugami M;Koya I;Furukawa T;Zhou L;Abe M;Sakimura K;Takebayashi H;Nakanishi A;Okano H;Yano M
早川矢野等人。表明 Qki5 通过介导大量 RNA 加工事件来调节神经干细胞之间的通讯。细胞类型特异性转录组是通过多种调节因子的作用实现的，这些调节因子经常在受限的组织区域内表达。在本研究中，我们确定了这样一个调节因子，Quaking 5 (Qki5)，它是一种 RNA 结合蛋白 (RNABP)，在早期胚胎神经干细胞中表达，随后在神经发生过程中下调。神经干细胞培养物中的 mRNA 测序分析表明，Qki 蛋白在神经干细胞转录组和可能由区域限制表达和亚细胞定位引起的各种形式的 mRNA 加工中发挥支持作用。此外，我们的子宫内电穿孔功能获得研究表明，核型 Qki 亚型 Qki5 支持神经干细胞状态。接下来，我们进行了体内转录组范围内的蛋白质-RNA相互作用作图，以寻找 Qki5 的直接靶点并阐明 Qki5 如何调节神经干细胞功能。结合我们的转录组分析，这种作图分析产生了单核苷酸分辨率的 Qki5-RNA 相互作用的真实图谱，鉴定了 892 个 Qki5 直接靶基因，以及发育中大脑中准确的 Qki5 依赖的选择性剪接规则。最后，我们的目标基因列表提供了第一个令人信服的证据，证明 Qki5 与特定的生物事件相关；即细胞与细胞的粘附。这一预测得到了对小鼠 Qki 蛋白基因消融的组织学分析的证实，该分析揭示了发育中大脑的侧壁顶面的破坏。这些数据共同表明，Qki5 通过介导大量 RNA 加工事件来调节神经干细胞之间的通讯，并表明剪接调节与神经干细胞状态之间存在新的联系。
Hayakawa-Yano et al. show that Qki5 regulates communication between neural stem cells by mediating numerous RNA processing events. Cell type-specific transcriptomes are enabled by the action of multiple regulators, which are frequently expressed within restricted tissue regions. In the present study, we identify one such regulator, Quaking 5 (Qki5), as an RNA-binding protein (RNABP) that is expressed in early embryonic neural stem cells and subsequently down-regulated during neurogenesis. mRNA sequencing analysis in neural stem cell culture indicates that Qki proteins play supporting roles in the neural stem cell transcriptome and various forms of mRNA processing that may result from regionally restricted expression and subcellular localization. Also, our in utero electroporation gain-of-function study suggests that the nuclear-type Qki isoform Qki5 supports the neural stem cell state. We next performed in vivo transcriptome-wide protein–RNA interaction mapping to search for direct targets of Qki5 and elucidate how Qki5 regulates neural stem cell function. Combined with our transcriptome analysis, this mapping analysis yielded a bona fide map of Qki5–RNA interaction at single-nucleotide resolution, the identification of 892 Qki5 direct target genes, and an accurate Qki5-dependent alternative splicing rule in the developing brain. Last, our target gene list provides the first compelling evidence that Qki5 is associated with specific biological events; namely, cell–cell adhesion. This prediction was confirmed by histological analysis of mice in which Qki proteins were genetically ablated, which revealed disruption of the apical surface of the lateral wall in the developing brain. These data collectively indicate that Qki5 regulates communication between neural stem cells by mediating numerous RNA processing events and suggest new links between splicing regulation and neural stem cell states.
登录
查看更多内容
影响因子：
64.5
作者：
Hafner M;Landthaler M;Burger L;Khorshid M;Hausser J;Berninger P;Rothballer A;Ascano M Jr;Jungkamp AC;Munschauer M;Ulrich A;Wardle GS;Dewell S;Zavolan M;Tuschl T
通讯作者：
Tuschl T
影响因子：
2.7
作者：
Chilov, Dmitri;Sinjushina, Natalia;Partanen, Juha
通讯作者：
Partanen, Juha
Gomafu lncRNA敲除小鼠表现出轻微的多动症，对心理刺激甲基苯丙胺的反应性增强。
影响因子：
4.6
作者：
Ip JY;Sone M;Nashiki C;Pan Q;Kitaichi K;Yanaka K;Abe T;Takao K;Miyakawa T;Blencowe BJ;Nakagawa S
通讯作者：
Nakagawa S
影响因子：
30.8
作者：
Ebersole, TA;Chen, Q;Artzt, K
通讯作者：
Artzt, K
影响因子：
2.7
作者：
AakuSaraste, E;Hellwig, A;Huttner, WB
通讯作者：
Huttner, WB