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

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

Author information

1
Center for Developmental Genetics, Department of Biology, New York University, 100 Washington Square East, New York, NY 10003, USA.
2
Center for Developmental Genetics, Department of Biology, New York University, 100 Washington Square East, New York, NY 10003, USA; Department of Applied Mathematics and Statistics, Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, NY 11794-5252, USA.
3
Departments of Biomedical Genetics and Neuroscience, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA.
4
Department of Molecular Biology and Genetics, Biotechnology 351, Cornell University, Ithaca, NY 14853-2703, USA.
5
Center for Developmental Genetics, Department of Biology, New York University, 100 Washington Square East, New York, NY 10003, USA; Arts & Sciences, New York University Shanghai, 1555 Century Ave., Pudong New Area, Shanghai 200122, China. Electronic address: david.fitch@nyu.edu.
6
Departments of Biomedical Genetics and Neuroscience, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA. Electronic address: douglas.portman@rochester.edu.

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.

KEYWORDS:

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

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