The Long Non-Coding RNA lep-5 Promotes the Juvenile-to-Adult Transition by Destabilizing LIN-28

Karin C. Kiontke, R. Antonio Herrera, Edward Vuong, Jintao Luo, Erich M. Schwarz, David H.A. Fitch, Douglas S. Portman

Research output: Contribution to journalArticlepeer-review

Abstract

Biological roles for most long non-coding RNAs (lncRNAs) remain mysterious. Here, using forward genetics, we identify lep-5, a lncRNA acting in the C. elegans heterochronic (developmental timing) pathway. Loss of lep-5 delays hypodermal maturation and male tail tip morphogenesis (TTM), hallmarks of the juvenile-to-adult transition. We find that lep-5 is a ∼600 nt cytoplasmic RNA that is conserved across Caenorhabditis and possesses three essential secondary structure motifs but no essential open reading frames. lep-5 expression is temporally controlled, peaking prior to TTM onset. Like the Makorin LEP-2, lep-5 facilitates the degradation of LIN-28, a conserved miRNA regulator specifying the juvenile state. Both LIN-28 and LEP-2 associate with lep-5 in vivo, suggesting that lep-5 directly regulates LIN-28 stability and may function as an RNA scaffold. These studies identify a key biological role for a lncRNA: by regulating protein stability, it provides a temporal cue to facilitate the juvenile-to-adult transition. The functions of most long non-coding RNAs (lncRNAs) are unknown, despite their abundance in biological systems. Here, by characterizing C. elegans mutants with developmental delays, Kiontke et al. identify lep-5, a ∼600-nt lncRNA. lep-5 regulates developmental timing by binding to and destabilizing LIN-28, a conserved regulator of miRNA biogenesis.

Original languageEnglish (US)
Pages (from-to)542-555.e9
JournalDevelopmental Cell
Volume49
Issue number4
DOIs
StatePublished - May 20 2019

Keywords

  • C. elegans
  • RNA scaffold
  • developmental timing
  • heterochronic
  • lincRNA
  • lncRNA
  • male tail
  • morphogenesis
  • ncRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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