Eye Center, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China.
ZhongMou Therapeutics, Wuhan, China.
Biochim Biophys Acta Mol Basis Dis. 2025 Jan;1871(1):167518. doi: 10.1016/j.bbadis.2024.167518. Epub 2024 Sep 20.
RNA-binding proteins (RBPs) play central roles in post-transcriptional gene regulation. However, the function of RBP in retinal progenitor cell differentiation and synaptic signal transmission are largely unexplored. Previously we have shown that Elavl2 regulates amacrine cell (AC) differentiation during retinogenesis, by directly binding to Nr4a2 and Barhl2. Elavl2 is expressed in early neuronal progenitors to mature neurons, and Elavl4 expression begins slightly later, during cortical neuron development as a paralog. Here, Retinal-specific Elavl2 and Elavl4 double knockout mice were made to further explore the role of Elavl2 and Elavl4 in retinal development and signal transduction. We disclose that Elavl4 binds to Satb1 to regulate Neurod1, then promoting retinal progenitor and amacrine cells differentiation. We were also surprised to find that Elavl2 interacted with GABA receptors at the RNA and protein levels. In conclusion, Elavl2 and Elavl4 regulate amacrine cells differentiation through different pathways, leading to decreased scotopic vision. Our findings reveal the roles of Elavl2 and Elavl4 in retinal amacrine cells differentiation in modulating visual functions.
RNA 结合蛋白(RBPs)在转录后基因调控中发挥核心作用。然而,RBP 在视网膜祖细胞分化和突触信号转导中的功能在很大程度上尚未被探索。我们之前已经表明,Elavl2 通过直接与 Nr4a2 和 Barhl2 结合来调节视网膜发生过程中的无长突细胞(amacrine cell,AC)分化。Elavl2 在早期神经元祖细胞到成熟神经元中表达,而 Elavl4 的表达开始稍晚,在皮质神经元发育过程中作为同源物开始表达。在这里,我们构建了视网膜特异性 Elavl2 和 Elavl4 双敲除小鼠,以进一步探索 Elavl2 和 Elavl4 在视网膜发育和信号转导中的作用。我们揭示了 Elavl4 通过与 Satb1 结合来调节 Neurod1,从而促进视网膜祖细胞和无长突细胞的分化。我们还惊讶地发现 Elavl2 在 RNA 和蛋白质水平上与 GABA 受体相互作用。总之,Elavl2 和 Elavl4 通过不同的途径调节无长突细胞的分化,导致暗视力下降。我们的研究结果揭示了 Elavl2 和 Elavl4 在调节视觉功能的视网膜无长突细胞分化中的作用。