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https://hdl.handle.net/2440/88421
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Type: | Journal article |
Title: | Neuronal elav-like (Hu) proteins regulate RNA splicing and abundance to control glutamate levels and neuronal excitability |
Author: | Ince-Dunn, G. Okano, H.J. Jensen, K.B. Park, W.-Y. Zhong, R. Ule, J. Mele, A. Fak, J.J. Yang, C. Zhang, C. Yoo, J. Herre, M. Okano, H. Noebels, J.L. Darnell, R.B. |
Citation: | Neuron, 2012; 75(6):1067-1080 |
Publisher: | Elsevier |
Issue Date: | 2012 |
ISSN: | 0896-6273 1097-4199 |
Statement of Responsibility: | Gulayse Ince-Dunn, Hirotaka J. Okano, Kirk B. Jensen, Woong-Yang Park, Ru Zhong, Jernej Ule, Aldo Mele, John J. Fak, ChingWen Yang, Chaolin Zhang, Jong Yoo, Margaret Herre, Hideyuki Okano, Jeffrey L. Noebels and Robert B. Darnell |
Abstract: | The paraneoplastic neurologic disorders target several families of neuron-specific RNA binding proteins (RNABPs), revealing that there are unique aspects of gene expression regulation in the mammalian brain. Here, we used HITS-CLIP to deter- mine robust binding sites targeted by the neuronal Elav-like (nElavl) RNABPs. Surprisingly, nElav protein binds preferentially to GU-rich sequences in vivo and in vitro, with secondary binding to AU-rich sequences. nElavl null mice were used to validate the consequence of these binding events in the brain, demonstrating that they bind intronic sequences in a position dependent manner to regulate alternative splicing and to 30 UTR sequences to regulate mRNA levels. These controls converge on the glutamate synthesis pathway in neurons; nElavl proteins are required to maintain neurotransmitter glutamate levels, and the lack of nElavl leads to spontaneous epileptic seizure activity. The genome-wide anal- ysis of nElavl targets reveals that one function of neuron-specific RNABPs is to control excitation-inhibition balance in the brain. |
Keywords: | Brain Neurons Animals Animals, Newborn Mice, Knockout Mice Epilepsy Disease Models, Animal Glutaminase Glutamic Acid RNA-Binding Proteins Nerve Tissue Proteins RNA, Messenger 3' Untranslated Regions Electroencephalography Microarray Analysis Computational Biology Gene Expression Regulation RNA Splicing ELAV Proteins |
Rights: | © 2012 Elsevier Inc. Published by Elsevier Inc. |
DOI: | 10.1016/j.neuron.2012.07.009 |
Grant ID: | K99GM95713 NS34389 |
Published version: | http://dx.doi.org/10.1016/j.neuron.2012.07.009 |
Appears in Collections: | Aurora harvest 2 Molecular and Biomedical Science publications |
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