Long noncoding RNA DREAMer bridges the DREAM complex and E2f1 to regulate endoreplication in Drosophila

Sci Adv. 2024 Nov 8;10(45):eadr4936. doi: 10.1126/sciadv.adr4936. Epub 2024 Nov 8.

Abstract

Rb/E2f and DREAM complexes play vital roles in regulating cell cycle progression. To date, how they coordinate their functions to regulate cell cycle-dependent gene expression is not clear. Here, we identified a long noncoding RNA (lncRNA), which we named DREAMer, that bridges the interaction between E2f1 and the dREAM complex to regulate endoreplication specifically in Drosophila salivary gland. We show that E2f1 directly stimulates DREAMer expression, whereas DREAMer mediates the repression of e2f1 transcription by modulating the recruitment of the dREAM complex to the e2f1 promoter via a direct interaction with the dREAM component E2f2. The depletion of DREAMer impairs dREAM binding, leading to derepression of e2f1 transcription, which ultimately increases E2f1 activity and promotes the endoreplication. Furthermore, the transcriptomic analysis revealed profound changes in cell cycle-related gene expression in DREAMerKO salivary glands. Together, our findings reveal an lncRNA-mediated link between the dREAM complex and E2f1, which regulates endoreplication during development.

MeSH terms

  • Animals
  • Caspases
  • Drosophila / genetics
  • Drosophila / metabolism
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • E2F1 Transcription Factor* / genetics
  • E2F1 Transcription Factor* / metabolism
  • E2F2 Transcription Factor / genetics
  • E2F2 Transcription Factor / metabolism
  • Gene Expression Regulation
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Salivary Glands / metabolism
  • Transcription Factors

Substances

  • RNA, Long Noncoding
  • E2F1 Transcription Factor
  • Drosophila Proteins
  • E2f1 protein, Drosophila
  • STRICA protein, Drosophila
  • E2F2 Transcription Factor
  • E2f2 protein, Drosophila
  • Transcription Factors
  • Caspases