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

Cell Rep. 2020 Mar 10;30(10):3339-3352.e6. doi: 10.1016/j.celrep.2020.02.047.

Abstract

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.

Keywords: 3’ UTR-mediated co-localization; Drosophila embryos; cen and ik2; centrosomal targeting; cis natural antisense transcripts; mRNA localization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Centrosome / metabolism*
  • Conserved Sequence
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Embryo, Nonmammalian / metabolism
  • Evolution, Molecular
  • Gene Expression Regulation
  • Humans
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism*
  • Oocytes / metabolism
  • Polyribosomes / metabolism
  • Protein Biosynthesis
  • RNA Transport
  • RNA, Antisense / genetics
  • RNA, Antisense / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • CEN protein, Drosophila
  • Drosophila Proteins
  • RNA, Antisense
  • RNA, Messenger
  • I-kappa B Kinase
  • IKKepsilon protein, Drosophila

Grants and funding