PMID- 21471000 OWN - NLM STAT- MEDLINE DCOM- 20110926 LR - 20211020 IS - 1939-4586 (Electronic) IS - 1059-1524 (Print) IS - 1059-1524 (Linking) VI - 22 IP - 11 DP - 2011 Jun 1 TI - In neurons, activity-dependent association of dendritically transported mRNA transcripts with the transacting factor CBF-A is mediated by A2RE/RTS elements. PG - 1864-77 LID - 10.1091/mbc.E10-11-0904 [doi] AB - In neurons certain mRNA transcripts are transported to synapses through mechanisms that are not fully understood. Here we report that the heterogeneous nuclear ribonucleoprotein CBF-A (CArG Box binding Factor A) facilitates dendritic transport and localization of activity-regulated cytoskeleton-associated protein (Arc), brain-derived neurotrophic factor (BDNF), and calmodulin-dependent protein kinase II (CaMKIIalpha) mRNAs. We discovered that, in the adult mouse brain, CBF-A has a broad distribution. In the nucleus, CBF-A was found at active transcription sites and interchromosomal spaces and close to nuclear pores. In the cytoplasm, CBF-A localized to dendrites as well as pre- and postsynaptic sites. CBF-A was found in synaptosomal fractions, associated with Arc, BDNF, and CaMKIIalpha mRNAs. Electrophoretic mobility shift assays demonstrated a direct interaction mediated via their hnRNP A2 response element (A2RE)/RNA trafficking sequence (RTS) elements located in the 3' untranslated regions. In situ hybridization and microscopy on live hippocampal neurons showed that CBF-A is in dynamic granules containing Arc, BDNF, and CaMKIIalpha mRNAs. N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) postsynaptic receptor stimulation led to CBF-A accumulation in dendrites; increased Arc, BDNF, and CaMKIIalpha mRNA levels; and increased amounts of transcripts coprecipitating with CBF-A. Finally, CBF-A gene knockdown led to decreased mRNA levels. We propose that CBF-A cotranscriptionally binds RTSs in Arc, BDNF, and CaMKIIalpha mRNAs and follows the transcripts from genes to dendrites, promoting activity-dependent nuclear sorting of transport-competent mRNAs. FAU - Raju, Chandrasekhar S AU - Raju CS AD - Department of Cell and Molecular Biology, Karolinska Institutet, S-171 77 Stockholm, Sweden. FAU - Fukuda, Nanaho AU - Fukuda N FAU - Lopez-Iglesias, Carmen AU - Lopez-Iglesias C FAU - Goritz, Christian AU - Goritz C FAU - Visa, Neus AU - Visa N FAU - Percipalle, Piergiorgio AU - Percipalle P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110406 PL - United States TA - Mol Biol Cell JT - Molecular biology of the cell JID - 9201390 RN - 0 (3' Untranslated Regions) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (CCAAT-Binding Factor) RN - 0 (Cytoskeletal Proteins) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Mtap2 protein, mouse) RN - 0 (Nerve Tissue Proteins) RN - 0 (Nfyb protein, mouse) RN - 0 (RNA, Messenger) RN - 0 (activity regulated cytoskeletal-associated protein) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2) SB - IM MH - *3' Untranslated Regions MH - Animals MH - Axons/metabolism/ultrastructure MH - Base Sequence MH - Brain-Derived Neurotrophic Factor/genetics MH - CCAAT-Binding Factor/genetics/*metabolism MH - Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics MH - Cell Culture Techniques MH - Cell Nucleus/metabolism/ultrastructure MH - Cells, Cultured MH - Cytoplasmic Granules/metabolism MH - Cytoskeletal Proteins/genetics MH - Dendrites/*metabolism MH - Hippocampus/cytology/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Microtubule-Associated Proteins/metabolism MH - Nerve Tissue Proteins/genetics MH - Neurons/*metabolism MH - Prosencephalon/cytology/metabolism MH - Protein Binding MH - RNA Interference MH - *RNA Transport MH - RNA, Messenger/*metabolism MH - Rats MH - Response Elements/*genetics MH - Synapses/metabolism/ultrastructure PMC - PMC3103402 EDAT- 2011/04/08 06:00 MHDA- 2011/09/29 06:00 PMCR- 2011/08/16 CRDT- 2011/04/08 06:00 PHST- 2011/04/08 06:00 [entrez] PHST- 2011/04/08 06:00 [pubmed] PHST- 2011/09/29 06:00 [medline] PHST- 2011/08/16 00:00 [pmc-release] AID - mbc.E10-11-0904 [pii] AID - E10-11-0904 [pii] AID - 10.1091/mbc.E10-11-0904 [doi] PST - ppublish SO - Mol Biol Cell. 2011 Jun 1;22(11):1864-77. doi: 10.1091/mbc.E10-11-0904. Epub 2011 Apr 6.