PT - JOURNAL ARTICLE AU - Huidong Wang AU - Anna Iacoangeli AU - Susanna Popp AU - Ilham A. Muslimov AU - Hiroaki Imataka AU - Nahum Sonenberg AU - Ivan B. Lomakin AU - Henri Tiedge TI - Dendritic BC1 RNA: Functional Role in Regulation of Translation Initiation AID - 10.1523/JNEUROSCI.22-23-10232.2002 DP - 2002 Dec 01 TA - The Journal of Neuroscience PG - 10232--10241 VI - 22 IP - 23 4099 - http://www.jneurosci.org/content/22/23/10232.short 4100 - http://www.jneurosci.org/content/22/23/10232.full SO - J. Neurosci.2002 Dec 01; 22 AB - In neurons, local protein synthesis in synaptodendritic microdomains has been implicated in the growth and plasticity of synapses. Prerequisites for local translation are the targeted transport of RNAs to distal sites of synthesis in dendrites and translational control mechanisms to limit synthesis to times of demand. Here we identify dendritic BC1 RNA as a specific repressor of translation. Experimental use of internal ribosome entry mechanisms and sucrose density gradient centrifugation showed that BC1-mediated repression targets translation at the level of initiation. Specifically, BC1 RNA inhibited formation of the 48S preinitiation complex, i.e., recruitment of the small ribosomal subunit to the messenger RNA (mRNA). However, 48S complex formation that is independent of the eukaryotic initiation factor 4 (eIF4) family of initiation factors was found to be refractory to inhibition by BC1 RNA, a result that implicates at least one of these factors in the BC1 repression pathway. Biochemical experiments indicated a specific interaction of BC1 RNA with eIF4A, an RNA unwinding factor, and with poly(A)-binding protein. Both proteins were found enriched in synaptodendritic microdomains. Significantly, BC1-mediated repression was shown to be effective not only in cap-dependent translation initiation but also in eIF4-dependent internal initiation. The results suggest a functional role of BC1 RNA as a mediator of translational control in local protein synthesis in nerve cells.