IRES-mediated translation of cofilin regulates axonal growth cone extension and turning

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.