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

Dev Cell. 2019 May 20;49(4):542-555.e9. doi: 10.1016/j.devcel.2019.03.003. Epub 2019 Apr 4.


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.

Keywords: C. elegans; RNA scaffold; developmental timing; heterochronic; lincRNA; lncRNA; male tail; morphogenesis; ncRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Morphogenesis / genetics
  • Morphogenesis / physiology
  • Mutation
  • Phenotype
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism
  • Transcription Factors / metabolism


  • Caenorhabditis elegans Proteins
  • LIN-28 protein, C elegans
  • RNA, Long Noncoding
  • Repressor Proteins
  • Ribonucleoproteins
  • Transcription Factors