Synaptic signaling and aberrant RNA splicing in autism spectrum disorders.
Synaptic signaling and aberrant RNA splicing in autism spectrum disorders.
复制标题
自闭症谱系中的突触信号传导和异常RNA剪接。
DOI：
10.3389/fnsyn.2011.00001
复制
发表时间：
2011
影响因子：
3.7
通讯作者：
Sadee W
中科院分区：
文献类型：
--
作者：
Smith RM;Sadee W
突触前和突触后细胞黏附分子之间的相互作用推动突触发育成熟。这些跨突触相互作用由CAM RNAs的选择性剪接调节，最终决定神经递质的表型。由选择性剪接产生的各种各样的RNA产生了无数的蛋白质亚型，这些蛋白质亚型是指导专门的细胞间连接所必需的。未能产生适当的突触黏附蛋白与谷氨酸和γ-氨基丁酸信号的中断有关，导致活动依赖的神经元可塑性丧失，并有发生发育障碍的风险，包括自闭症。虽然目前与自闭症相关的大多数基因突变都是罕见的变异，可以改变突触候选基因的蛋白质编码序列，但影响结构性和选择性剪接的调节性多态已经成为许多其他疾病的风险因素，估计占一般疾病风险的40%-60%。在这里，我们回顾了突触相关基因的RNA剪接异常与自闭症谱系障碍的关系。
Interactions between presynaptic and postsynaptic cellular adhesion molecules (CAMs) drive synapse maturation during development. These trans-synaptic interactions are regulated by alternative splicing of CAM RNAs, which ultimately determines neurotransmitter phenotype. The diverse assortment of RNAs produced by alternative splicing generates countless protein isoforms necessary for guiding specialized cell-to-cell connectivity. Failure to generate the appropriate synaptic adhesion proteins is associated with disrupted glutamatergic and gamma-aminobutyric acid signaling, resulting in loss of activity-dependent neuronal plasticity, and risk for developmental disorders, including autism. While the majority of genetic mutations currently linked to autism are rare variants that change the protein-coding sequence of synaptic candidate genes, regulatory polymorphisms affecting constitutive and alternative splicing have emerged as risk factors in numerous other diseases, accounting for an estimated 40–60% of general disease risk. Here, we review the relationship between aberrant RNA splicing of synapse-related genes and autism spectrum disorders.