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 language | English (US) |
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Pages (from-to) | 542-555.e9 |
Journal | Developmental Cell |
Volume | 49 |
Issue number | 4 |
DOIs | |
State | Published - May 20 2019 |
Keywords
- C. elegans
- RNA scaffold
- developmental timing
- heterochronic
- lincRNA
- lncRNA
- male tail
- morphogenesis
- ncRNA
ASJC Scopus subject areas
- Molecular Biology
- General Biochemistry, Genetics and Molecular Biology
- Developmental Biology
- Cell Biology