The Function Studies Of MicroRNAs Related To Autism Susceptibility Genes

Autism is a subtype of pervasive developmental disorder which is characterized by language disorders, impaired social interaction, narrow interests and rigid repetition. The cause of Autism has not been known clearly, but studies show that genetic factors play an important role.microRNAs (miRNAs) are a kind of 20-25 nt, noncoding RNAs that function as post-transcriptional repressors often by binding to the 3'UTR of targeted mRNA and leading to their degradation or translational repression. Previous studies show that miRNAs play an important role in cell differentiation, neuronal polarity, embryogenesis and tumor genesis.Our lab has collected autism susceptibility genes and established miR-34 mutant flies previously. SEMA5A, SHANK3, CNTNAP2 are autism susceptibility genes in human, this study focuses on the homologous genes in Drosophila (Sema-5c, ProSAP, Nrx-IV), in vitro study has found miR-34 can interact with these autism susceptibility genes directly. Based on these results, further research is needed to find out the function of miR-34 in Drosophila central nervous system, and relationship between miR-34 and these autism susceptibility genes in vivo.Firstly, miR-34 knockout flies have a distinctly weaker mobility and shorten life span, miR-34 overexpression flies show abnormally development in adult stage.Secondly, the NMJ4 button number and button area of miR-34 knockout 3rd larva shows a significant reduction, while the miR-34 overexpression flies display the opposite tendency.Thirdly, dual-Iuciferase assay is conducted to assess whether the genes could interact with miR-34 in vitro. The results of ProSAP, Sema-5c, Nrx-? are positive.Lastly, an opposite expression pattern is showing between Nrx-IV and miR-34 in both mRNA and protein expression level.In conclusion, Nrx-IV is a target gene of miR-34.