The RNA binding protein HuR determines the differential translation of autism-associated FoxP subfamily members in the developing neocortex.
The RNA binding protein HuR determines the differential translation of autism-associated FoxP subfamily members in the developing neocortex.
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DOI：
10.1038/srep28998
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发表时间：
2016-07-07
影响因子：
4.6
通讯作者：
Rasin MR
中科院分区：
文献类型：
--
作者：
Popovitchenko T;Thompson K;Viljetic B;Jiao X;Kontonyiannis DL;Kiledjian M;Hart RP;Rasin MR
包含家族成员的叉头盒结构域(FOX)已知在新皮质生成中发挥作用，也与自闭症谱系上的疾病有关。在这里，我们证明了单一的RNA结合蛋白，HU抗原R(HUR)，决定了结合的mRNAs的翻译特异性，并足以定义不同的FoxP特征的新皮质投射神经元亚群。此外，Hur不同的磷酸化状态在体外对FoxP mRNAs的翻译有不同的调节作用。这证明了RNA结合蛋白在发育中的大脑框架内的重要性，并进一步证实了mRNA翻译在自闭症发病机制中的作用。
Forkhead-box domain (Fox) containing family members are known to play a role in neocorticogenesis and have also been associated with disorders on the autism spectrum. Here we show that a single RNA-binding protein, Hu antigen R (HuR), dictates translation specificity of bound mRNAs and is sufficient to define distinct Foxp-characterized subpopulations of neocortical projection neurons. Furthermore, distinct phosphorylation states of HuR differentially regulate translation of Foxp mRNAs in vitro. This demonstrates the importance of RNA binding proteins within the framework of the developing brain and further confirms the role of mRNA translation in autism pathogenesis.