In silico investigation of Aedes aegypti male-determining factor (NIX): RNA recognition motif-3, structural model and selective nucleic acid binding mode.

Abstract

Mosquito borne viruses and their corresponding human infections have a fast growing impact on worldwide public health systems; in particular, Aedes aegypti and Aedes albopictus are transmitting these viruses. Only female mosquitoes bite and spread diseases. Male development in A. aegypti is initiated by male determining factors. These factors are potential candidates for the implementation of vector control strategies. Where at an early stage in gender development female mosquitoes are converted into harmless males. Among these factors, a novel gene, NIX, has been identified that shares moderate identity with transformer-2, one of the key sex-determination genes in Drosophila melanogaster. Hall et al. 2015 described two RNA recognition motifs (RRMs) in the NIX sequence, but a UniProt database search showed that A. aegypti NIX contains three RNA RRM. A homology model of NIX_RRM-3 was generated to investigate the interaction with RNA using molecular dynamics simulations. The sequence AGACGU was the most interesting result. During the binding process A1, G2 and G5 adopt an unusual syn conformation. The results let assume that the C-terminus of NIX_RRM-3 is involved in the recognition process of the target RNA motif (e.g. AG) and controls the interaction between target RNA and A. aegypti NIX.