miR-92a Suppresses Mushroom Body-Dependent Memory Consolidation in Drosophila

Abstract

MicroRNAs fine tune gene expression to regulate many aspects of nervous system physiology. Here, we show that miR-92a suppresses memory consolidation that occurs in the αβ and γ mushroom body neurons of Drosophila, making miR-92a a memory suppressor microRNA. Bioinformatics analyses suggested that mRNAs encoding kinesin heavy chain 73 (Khc73), a protein that belongs to Kinesin-3 family of anterograde motor proteins, may be a functional target of miR-92a. Behavioral studies that employed expression of khc73 with and without its 3’UTR containing miR-92a target sites, luciferase assays in HEK cells with reporters containing wild-type and mutant target sequences in the khc73 3’ UTR, and immunohistochemistry experiments involving Khc73 expression with and without the wild-type khc73 3’UTR all point to the conclusion that khc73 is a major target of miR-92a in its functional role as a microRNA memory suppressor gene.

SIGNIFICANCE STATEMENT Much remains to be learned about how microRNAs regulate gene expression for cognitive processes such as memory formation. The important questions include which of the many different microRNAs are involved, what are their targets, and what specific aspects of memory formation do they regulate? Here we show that the microRNA, miR-92a, normally functions to suppress the consolidation of memories by repressing the expression of a specific kinesin molecule, khc73, in the mushroom body neurons of the Drosophila brain.