title: HuD promotes BDNF expression in brain neurons via selective stabilization of the BDNF long 3'UTR mRNA.
abstract: Complex regulation of brain-derived neurotrophic factor (BDNF) governs its intricate functions in brain development and neuronal plasticity. Besides tight transcriptional control from multiple distinct promoters, alternative 3'end processing of the BDNF transcripts generates either a long or a short 3'untranslated region (3'UTR). Previous reports indicate that distinct RNA sequence in the BDNF 3'UTRs differentially regulates BDNF production in the brain to accommodate neuronal activity changes, conceivably through differential interactions with undefined trans-acting factors that regulate stability and translation of these BDNF mRNA isoforms. In this study, we report that the neuronal RNA-binding protein (RBP) HuD interacts with a highly conserved AU-rich element (ARE) specifically located in the BDNF long 3'UTR. Such interaction is necessary and sufficient for selective stabilization of mRNAs that contain the BDNF long 3'UTR in vitro and in vivo. Moreover, in a HuD transgenic mouse model, the BDNF long 3'UTR mRNA is increased in the hippocampal dentate granule cells (DGCs), leading to elevated expression of BDNF protein that is transported and stored in the mossy fiber (MF) terminals. Our results identify HuD as the first trans-acting factor that enhances BDNF expression specifically through the long 3'UTR and a novel mechanism that regulates BDNF protein production in selected neuronal populations by HuD abundance.
authors: Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors: Megan
authors: M
authors: Allen
authors: Clark
authors: C
authors: Bird
authors: Wei
authors: W
authors: Feng
authors: Guanglu
authors: G
authors: Liu
authors: Wenqi
authors: W
authors: Li
authors: Nora I
authors: NI
authors: Perrone-Bizzozero
authors: Yue
authors: Y
authors: Feng
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D051959:ELAV Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D020218:Response Elements
chemical_list: D020413:3' Untranslated Regions; D019208:Brain-Derived Neurotrophic Factor; D051959:ELAV Proteins; D012333:RNA, Messenger
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