| First Author | Ince-Dunn G | Year | 2012 |
| Journal | Neuron | Volume | 75 |
| Issue | 6 | Pages | 1067-80 |
| PubMed ID | 22998874 | Mgi Jnum | J:188326 |
| Mgi Id | MGI:5440337 | Doi | 10.1016/j.neuron.2012.07.009 |
| Citation | Ince-Dunn G, et al. (2012) Neuronal Elav-like (Hu) Proteins Regulate RNA Splicing and Abundance to Control Glutamate Levels and Neuronal Excitability. Neuron 75(6):1067-80 |
| abstractText | 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 determine 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 3'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 analysis of nElavl targets reveals that one function of neuron-specific RNABPs is to control excitation-inhibition balance in the brain. VIDEO ABSTRACT: |
