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

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.