Vicario Annalisa, Colliva Andrea, Ratti Antonia, Davidovic Laetitia, Baj Gabriele, Gricman Łukasz, Colombrita Claudia, Pallavicini Alberto, Jones Kevin R, Bardoni Barbara, Tongiorgi Enrico
Department of Life Sciences, University of Trieste Trieste, Italy.
Laboratory of Neuroscience - IRCCS Istituto Auxologico Italiano Milano, Italy ; Department of Pathophysiology and Transplantation, "Dino Ferrari Center", Università degli Studi di Milano Milano, Italy.
Front Mol Neurosci. 2015 Oct 29;8:62. doi: 10.3389/fnmol.2015.00062. eCollection 2015.
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.
mRNA在神经元树突中的分选依赖于可诱导的转运机制,但其分子基础尚不清楚。我们在此以大鼠脑源性神经营养因子(BDNF)mRNA的可诱导树突靶向机制为例进行研究。BDNF编码具有短或长3'UTR的多种mRNA,两者都被假设含有可诱导的树突靶向信号。然而,两种3'UTR异构体的分选机制存在争议。我们发现,具有短3'UTR的BDNF mRNA的树突定位在体外由去极化和NT3诱导,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的树突靶向由活性或BDNF诱导,并且需要CPEB-1以及由ELAV-1、-3、-4和FXR蛋白介导的胞体保留信号的解除。因此,长和短3'UTR通过使用不同的RNA结合蛋白集,提供了一种响应不同刺激的选择性靶向机制,这可能是BDNF变体在神经元发育和可塑性中不同作用的基础。