Inter-dependent Centrosomal Co-localization of the cen and ik2 cis-Natural Antisense mRNAs in Drosophila

Abstract

Summary: Overlapping genes are prevalent in most genomes, but the extent to which this organization influences regulatory events operating at the post-transcriptional level remains unclear. Studying the cen and ik2 genes of Drosophila melanogaster, which are convergently transcribed as cis-natural antisense transcripts (cis-NATs) with overlapping 3′ UTRs, we found that their encoded mRNAs strikingly co-localize to centrosomes. These transcripts physically interact in a 3′ UTR-dependent manner, and the targeting of ik2 requires its 3′ UTR sequence and the presence of cen mRNA, which serves as the main driver of centrosomal co-localization. The cen transcript undergoes localized translation in proximity to centrosomes, and its localization is perturbed by polysome-disrupting drugs. By interrogating global fractionation-sequencing datasets generated from Drosophila and human cellular models, we find that RNAs expressed as cis-NATs tend to co-localize to specific subcellular fractions. This work suggests that post-transcriptional interactions between RNAs with complementary sequences can dictate their localization fate in the cytoplasm. : Bergalet et al. characterize an example of cis-natural antisense mRNA transcripts that inter-dependently co-localize to cytoplasmic centrosomes through an interaction mediated by their 3′ UTRs. Keywords: mRNA localization, cis natural antisense transcripts, 3’ UTR-mediated co-localization, cen and ik2, centrosomal targeting, Drosophila embryos