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IRES‐mediated translation of cofilin regulates axonal growth cone extension and turning
Authors:Jung‐Hyun Choi  Wei Wang  Dongkeun Park  Sung‐Hoon Kim  Kyong‐Tai Kim  Kyung‐Tai Min
Affiliation:1. Department of Life Sciences, Pohang University of Science and Technology, Pohang, Korea;2. Department of Biological Sciences, School of Life Sciences, Ulsan, Korea;3. National Creative Research Initiative Center for Proteostasis, Ulsan National Institute of Science and Technology, Ulsan, Korea;4. Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea
Abstract: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 insights into the function of IRES‐mediated translation in neuronal development.
Keywords:axonal growth cone  cofilin  internal ribosome entry sites
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