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 Fitch, Douglas S. Portman

Research output: Contribution to journalArticle

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

Fingerprint

Long Noncoding RNA
MicroRNAs
Morphogenesis
Tail
Caenorhabditis
RNA
Protein Stability
Biological systems
Scaffolds
Open Reading Frames
Cues
Degradation
Proteins

Keywords

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

ASJC Scopus subject areas

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

Cite this

Kiontke, K. C., Herrera, R. A., Vuong, E., Luo, J., Schwarz, E. M., Fitch, D., & Portman, D. S. (2019). The Long Non-Coding RNA lep-5 Promotes the Juvenile-to-Adult Transition by Destabilizing LIN-28. Developmental Cell, 49(4), 542-555.e9. https://doi.org/10.1016/j.devcel.2019.03.003

The Long Non-Coding RNA lep-5 Promotes the Juvenile-to-Adult Transition by Destabilizing LIN-28. / Kiontke, Karin C.; Herrera, R. Antonio; Vuong, Edward; Luo, Jintao; Schwarz, Erich M.; Fitch, David; Portman, Douglas S.

In: Developmental Cell, Vol. 49, No. 4, 20.05.2019, p. 542-555.e9.

Research output: Contribution to journalArticle

Kiontke, KC, Herrera, RA, Vuong, E, Luo, J, Schwarz, EM, Fitch, D & Portman, DS 2019, 'The Long Non-Coding RNA lep-5 Promotes the Juvenile-to-Adult Transition by Destabilizing LIN-28', Developmental Cell, vol. 49, no. 4, pp. 542-555.e9. https://doi.org/10.1016/j.devcel.2019.03.003
Kiontke, Karin C. ; Herrera, R. Antonio ; Vuong, Edward ; Luo, Jintao ; Schwarz, Erich M. ; Fitch, David ; Portman, Douglas S. / The Long Non-Coding RNA lep-5 Promotes the Juvenile-to-Adult Transition by Destabilizing LIN-28. In: Developmental Cell. 2019 ; Vol. 49, No. 4. pp. 542-555.e9.
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