期刊
EMBO JOURNAL
卷 37, 期 5, 页码 -出版社
WILEY
DOI: 10.15252/embj.201695266
关键词
axonal growth cone; cofilin; internal ribosome entry sites
资金
- Leading Research Program, National Research Foundation of Korea (NRF) - Korean government (MEST) [2016R1A3B1905982]
- BK21 Plus - Ministry of Education, Science and Technology [10Z20130012243]
- Brain Research Program through the National Research Foundation of Korea (NRF) [2017023478]
- KBRI Basic Research Program through Korea Brain Research Institute (KBRI) - Ministry of Science, ICT and Future Planning [17-BR-01]
- Cooperative Research Program for Agriculture Science and Technology Development of the Rural Development Administration, Korea [PJ01121602]
- Ministry of Science & ICT (MSIT), Republic of Korea [17-BR-01] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2016R1A3B1905982] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
In neuronal development, dynamic rearrangement of actin promotes axonal growth cone extension, and spatiotemporal translation of local mRNAs in response to guidance cues directs axonal growth cone steering, where cofilin plays a critical role. While regulation of cofilin activity is well studied, regulatory mechanism for cofilin mRNA translation in neurons is unknown. In eukaryotic cells, proteins can be synthesized by cap-dependent or cap-independent mechanism via internal ribosome entry site (IRES)-mediated translation. IRES-mediated translation has been reported in various pathophysiological conditions, but its role in normal physiological environment is poorly understood. Here, we report that 5'UTR of cofilin mRNA contains an IRES element, and cofilin is predominantly translated by IRES-mediated mechanism in neurons. Furthermore, we show that IRES-mediated translation of cofilin is required for both axon extension and axonal growth cone steering. Our results provide new insightsinto the function of IRES-mediated translation in neuronal development.
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