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J. Biol. Chem., Vol. 279, Issue 51, 53427-53434, December 17, 2004

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An RNA-interacting Protein, SYNCRIP (Heterogeneous Nuclear Ribonuclear Protein Q1/NSAP1) Is a Component of mRNA Granule Transported with Inositol 1,4,5-Trisphosphate Receptor Type 1 mRNA in Neuronal Dendrites^*

Hiroko Bannai, Kazumi Fukatsu, Akihiro Mizutani¶, Tohru Natsume||, Shun-ichiro Iemura||, Tohru Ikegami, Takafumi Inoue¶**, and Katsuhiko Mikoshiba¶

From the Laboratory for Developmental Neurobiology, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan, Division of Molecular Neurobiology and Division of Neural Signal Information NTT-IMSUT, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 Japan, ^¶Calcium Oscillation Project, ICORP, Japan Science and Technology Corp., 3-4-4 Shirokanedai, Minato-ku, Tokyo 108-0071, Japan, and ^||National Institute of Advanced Industrial Science and Technology, Biological Information Research Center, 2-41-6 Ohmi, Kohtoh-ku, Tokyo 135-0064, Japan

mRNA transport and local translation in the neuronal dendrite is implicated in the induction of synaptic plasticity. Recently, we cloned an RNA-interacting protein, SYNCRIP (heterogeneous nuclear ribonuclear protein Q1/NSAP1), that is suggested to be important for the stabilization of mRNA. We report here that SYNCRIP is a component of mRNA granules in rat hippocampal neurons. SYNCRIP was mainly found at cell bodies, but punctate expression patterns in the proximal dendrite were also seen. Time-lapse analysis in living neurons revealed that the granules labeled with fluorescent protein-tagged SYNCRIP were transported bi-directionally within the dendrite at 0.05 µm/s. Treatment of neurons with nocodazole significantly inhibited the movement of green fluorescent protein-SYNCRIP-positive granules, indicating that the transport of SYNCRIP-containing granules is dependent on microtubules. The distribution of SYNCRIP-containing granules overlapped with that of dendritic RNAs and elongation factor 1. SYNCRIP was also found to be co-transported with green fluorescent protein-tagged human staufen1 and the 3'-untranslated region of inositol 1,4,5-trisphosphate receptor type 1 mRNA. These results suggest that SYNCRIP is transported within the dendrite as a component of mRNA granules and raise the possibility that mRNA turnover in mRNA granules and the regulation of local protein synthesis in neuronal dendrites may involve SYNCRIP.

Received for publication, August 24, 2004 , and in revised form, October 5, 2004.

^* This study was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (to T. Inoue and K. M.), the Ministry of Health, Labor, and Welfare of Japan (to T. Inoue), and the 21st Century Center of Excellence Program, Center for Integrated Brain Medical Science from MEXT of Japan (to K. F.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Table SI, supplemental Data S1, and the legends for supplemental Movies 1–3.

^** To whom correspondence should be addressed: Division of Molecular Neurobiology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo, 108-8639, Japan. Tel.: 81-3-5449-5320; Fax: 81-3-5449-5420; E-mail: tinoue{at}ims.u-tokyo.ac.jp.

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