Translational Inhibition of α-Neurexin 2

Neurexins are extensively investigated presynaptic cell-adhesion molecules which play important roles in transmitting signals and processing information at synapses that connect neurons into a vast network of cellular communications. Synaptic transmission of information is a fast and dynamic process which relies on rapid and tight regulation of synaptic protein expression. However, the mechanism underlying those regulation is still not fully understood. Therefore, we explore how the expression of NRXN2α, one of encoding genes for neurexins, is regulated at the translational level. NRXN2α transcript has a long and conserved 5'-untranslated region (5'UTR) suggestive of the rapid regulation of protein expression at the translational level. We first demonstrate that the 5'UTR has negative effects on the expression of the NRXN2α and find a critical subregion responsible for the major inhibitory function. Then we identify a particular secondary structure of G-quadruplex in the 5'UTR. Moreover, we find that the synergistic roles of G-quadruplex and upstream AUGs are responsible for most of NRXN2α-5'UTR inhibitory effects. In conclusion, we uncovered 5' UTR of neurexin2 potentially inhibits neurexin2 translation by multiple mechanisms. In addition, this study underscores the importance of direct protein quantitation in experiments rather than using mRNA as an indirect estimate of protein expression.