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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
Statement of
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.
RMID: 0030008379
DOI: 10.1016/j.neuron.2012.07.009
Appears in Collections:Molecular and Biomedical Science publications

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