Abstract: |
How are diverse regulatory strategies integrated to impose appropriately patterned gene expression that underlie in vivo phenotypes? Here, we reveal how coordinated miRNA regulation and neural-specific alternative polyadenylation (APA) of a single locus controls complex behaviors. Our entry was the unexpected observation that deletion of Bithorax complex (BX-C) miRNAs converts virgin female flies into a subjective post-mated behavioral state, normally induced by seminal proteins following copulation. Strikingly, this behavioral switch is directly attributable to misregulation of homothorax (hth). We localize specific CNS abdominal neurons where de-repressed Hth compromises virgin behavior in BX-C miRNA mutants. Moreover, we use genome engineering to demonstrate that precise mutation of hth 3′ UTR sites for BX-C miRNAs or deletion of its neural 3′ UTR extension containing most of these sites both induce post-mated behaviors in virgins. Thus, facilitation of miRNA-mediated repression by neural APA is required for virgin females to execute behaviors appropriate to their internal state. © 2020 Elsevier Inc. Garaulet et al. show that two post-transcriptional regulatory pathways—miRNAs and alternative polyadenylation—intersect in the central nervous system to control a behavioral switch. Regulation of homothorax by the mir-iab-4/8 locus, preferentially via the neural 3′ UTR extension, is required for females to interpret the virgin behavioral state. © 2020 Elsevier Inc. |