PMID- 23383270 OWN - NLM STAT- MEDLINE DCOM- 20130717 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 1 DP - 2013 TI - HuD promotes BDNF expression in brain neurons via selective stabilization of the BDNF long 3'UTR mRNA. PG - e55718 LID - 10.1371/journal.pone.0055718 [doi] LID - e55718 AB - 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. FAU - Allen, Megan AU - Allen M AD - Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia, United States of America. FAU - Bird, Clark AU - Bird C FAU - Feng, Wei AU - Feng W FAU - Liu, Guanglu AU - Liu G FAU - Li, Wenqi AU - Li W FAU - Perrone-Bizzozero, Nora I AU - Perrone-Bizzozero NI FAU - Feng, Yue AU - Feng Y LA - eng GR - 5T32GM008602/GM/NIGMS NIH HHS/United States GR - R01 NS030255/NS/NINDS NIH HHS/United States GR - 5R01NS070526/NS/NINDS NIH HHS/United States GR - R01 DA034097/DA/NIDA NIH HHS/United States GR - R21 DA034452/DA/NIDA NIH HHS/United States GR - 1R01DA034097/DA/NIDA NIH HHS/United States GR - 5R01NS030255/NS/NINDS NIH HHS/United States GR - R01 NS070526/NS/NINDS NIH HHS/United States GR - T32 GM008367/GM/NIGMS NIH HHS/United States GR - T32 GM008602/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20130131 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (3' Untranslated Regions) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (ELAV Proteins) RN - 0 (RNA, Messenger) SB - IM MH - *3' Untranslated Regions MH - Animals MH - Base Sequence MH - Brain/*metabolism MH - Brain-Derived Neurotrophic Factor/*genetics/metabolism MH - Cells, Cultured MH - ELAV Proteins/*metabolism MH - Gene Expression Regulation MH - Genes, Reporter MH - Hippocampus/metabolism MH - Mice MH - Neurons/*metabolism MH - Protein Binding MH - RNA Interference MH - *RNA Stability MH - RNA, Messenger/*metabolism MH - Response Elements PMC - PMC3561324 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2013/02/06 06:00 MHDA- 2013/07/19 06:00 PMCR- 2013/01/31 CRDT- 2013/02/06 06:00 PHST- 2012/09/11 00:00 [received] PHST- 2012/12/29 00:00 [accepted] PHST- 2013/02/06 06:00 [entrez] PHST- 2013/02/06 06:00 [pubmed] PHST- 2013/07/19 06:00 [medline] PHST- 2013/01/31 00:00 [pmc-release] AID - PONE-D-12-27865 [pii] AID - 10.1371/journal.pone.0055718 [doi] PST - ppublish SO - PLoS One. 2013;8(1):e55718. doi: 10.1371/journal.pone.0055718. Epub 2013 Jan 31.