Barbee Scott A, Estes Patricia S, Cziko Anne-Marie, Hillebrand Jens, Luedeman Rene A, Coller Jeff M, Johnson Nick, Howlett Iris C, Geng Cuiyun, Ueda Ryu, Brand Andrea H, Newbury Sarah F, Wilhelm James E, Levine Richard B, Nakamura Akira, Parker Roy, Ramaswami Mani
Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721, USA.
Neuron. 2006 Dec 21;52(6):997-1009. doi: 10.1016/j.neuron.2006.10.028.
Local control of mRNA translation modulates neuronal development, synaptic plasticity, and memory formation. A poorly understood aspect of this control is the role and composition of ribonucleoprotein (RNP) particles that mediate transport and translation of neuronal RNAs. Here, we show that staufen- and FMRP-containing RNPs in Drosophila neurons contain proteins also present in somatic "P bodies," including the RNA-degradative enzymes Dcp1p and Xrn1p/Pacman and crucial components of miRNA (argonaute), NMD (Upf1p), and general translational repression (Dhh1p/Me31B) pathways. Drosophila Me31B is shown to participate (1) with an FMRP-associated, P body protein (Scd6p/trailer hitch) in FMRP-driven, argonaute-dependent translational repression in developing eye imaginal discs; (2) in dendritic elaboration of larval sensory neurons; and (3) in bantam miRNA-mediated translational repression in wing imaginal discs. These results argue for a conserved mechanism of translational control critical to neuronal function and open up new experimental avenues for understanding the regulation of mRNA function within neurons.
mRNA翻译的局部调控可调节神经元发育、突触可塑性和记忆形成。这种调控中一个尚未被充分理解的方面是介导神经元RNA运输和翻译的核糖核蛋白（RNP）颗粒的作用和组成。在这里，我们表明果蝇神经元中含有Staufen和FMRP的RNP包含一些也存在于体细胞“P小体”中的蛋白质，包括RNA降解酶Dcp1p和Xrn1p/Pacman以及miRNA（AGO）、NMD（Upf1p）和一般翻译抑制（Dhh1p/Me31B）途径的关键成分。果蝇Me31B被证明（1）与FMRP相关的P小体蛋白（Scd6p/拖车挂钩）一起参与发育中的眼成虫盘的FMRP驱动的、AGO依赖的翻译抑制；（2）参与幼虫感觉神经元的树突形成；（3）参与翅成虫盘中bantam miRNA介导的翻译抑制。这些结果表明存在一种对神经元功能至关重要的保守翻译控制机制，并为理解神经元内mRNA功能的调控开辟了新的实验途径。
