Bergalet, J., Patel, D., Legendre, F., Lapointe, C., Benoit Bouvrette, L.P., Chin, A., Blanchette, M., Kwon, E., Lécuyer, E. (2020). Inter-dependent Centrosomal Co-localization of the cen and ik2 cis-Natural Antisense mRNAs in Drosophila.  Cell Rep. 30(10): 3339--3352.e6.

FBrf0245098

Research paper

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.