Dendritic targeting of short and long 3' UTR BDNF mRNA is regulated by BDNF or NT-3 and distinct sets of RNA-binding proteins.
Dendritic targeting of short and long 3' UTR BDNF mRNA is regulated by BDNF or NT-3 and distinct sets of RNA-binding proteins.
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DOI：
10.3389/fnmol.2015.00062
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发表时间：
2015
影响因子：
4.8
通讯作者：
Tongiorgi E
中科院分区：
文献类型：
--
作者：
Vicario A;Colliva A;Ratti A;Davidovic L;Baj G;Gricman Ł;Colombrita C;Pallavicini A;Jones KR;Bardoni B;Tongiorgi E
神经元树突中mRNA的分选依赖于诱导型转运机制，其分子基础知之甚少。作为一个典型的例子，我们在这里研究了大鼠脑源性神经营养因子（BDNF）mRNA的诱导树突靶向机制。BDNF编码多个具有短或长3′ UTR的mRNA，这两种mRNA都被假设为具有诱导性树突靶向信号。然而，这两种3′ UTR异构体的分选机制仍存在争议。我们发现，具有短3′ UTR的BDNF mRNAs的树突状定位在体外由去极化和NT 3或在体内由癫痫发作诱导，并且需要CPEB-1，-2和ELAV-2，-4。长3′ UTR的树突状靶向由活性或BDNF诱导，需要CPEB-1和ELAV-1、-3、-4和FXR蛋白介导的体细胞滞留信号的缓解。因此，长和短的3′ UTR通过使用不同的RNA结合蛋白提供了响应不同刺激的选择性靶向机制，这可能解释了BDNF变体在神经元发育和可塑性中的不同作用。
Sorting of mRNAs in neuronal dendrites relies upon inducible transport mechanisms whose molecular bases are poorly understood. We investigated here the mechanism of inducible dendritic targeting of rat brain-derived neurotrophic factor (BDNF) mRNAs as a paradigmatic example. BDNF encodes multiple mRNAs with either short or long 3′ UTR, both hypothesized to harbor inducible dendritic targeting signals. However, the mechanisms of sorting of the two 3′ UTR isoforms are controversial. We found that dendritic localization of BDNF mRNAs with short 3′ UTR was induced by depolarization and NT3 in vitro or by seizures in vivo and required CPEB-1, -2 and ELAV-2, -4. Dendritic targeting of long 3′ UTR was induced by activity or BDNF and required CPEB-1 and the relief of soma-retention signals mediated by ELAV-1, -3, -4, and FXR proteins. Thus, long and short 3′ UTRs, by using different sets of RNA-binding proteins provide a mechanism of selective targeting in response to different stimuli which may underlay distinct roles of BDNF variants in neuronal development and plasticity.