@article{d4c808fbe2c14a839440c9446633c5f5,
title = "The Long Non-Coding RNA lep-5 Promotes the Juvenile-to-Adult Transition by Destabilizing LIN-28",
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.",
keywords = "C. elegans, RNA scaffold, developmental timing, heterochronic, lincRNA, lncRNA, male tail, morphogenesis, ncRNA",
author = "Kiontke, {Karin C.} and Herrera, {R. Antonio} and Edward Vuong and Jintao Luo and Schwarz, {Erich M.} and Fitch, {David H.A.} and Portman, {Douglas S.}",
note = "Funding Information: We thank K. Nguyen and K.Y. Lee for technical help in the screens yielding ny10 and fs8, respectively, and A. Woronik for help with statistical analyses. We thank V. Ambros, G. Ruvkun, T. Montgomery, D. Mathews, S. Bellaousov, A. Mason, A. Samuelson, L. Maquat, D. Moerman, C. Hammel, S. West, and WormBase for constructive discussions and information; F. Slack, V. Ambros, and A. Rougvie for strains; and E. Moss for generously providing the LIN-28 antibody. Some strains were provided by the Caenorhabditis Genetics Center (University of Minnesota), which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440). This research was supported by NIH R01 GM100140, NSF DEB 0922012, NYU RCF 002456, and research funds from NYU Shanghai (D.H.A.F.) and NIH R01 GM108885 and NSF IOS 1353075 (D.S.P.). E.V. was supported by the University of Rochester Medical Scientist Training Program, NIH T32 GM007356, and R.A.H. was supported by the New York Consortium for the Advancement of Postdoctoral Scholars, NIH K12 GM102778. Conceptualization, K.C.K. D.S.P. R.A.H. E.M.S. E.V. and D.H.A.F.; Methodology, R.A.H. K.C.K. J.L. D.S.P. E.M.S. and E.V.; Investigation, R.A.H. K.C.K. J.L. D.S.P. E.M.S. and E.V.; Original Draft, K.C.K. E.V. and D.S.P.; Review & Editing, D.H.A.F. K.C.K. D.S.P. and E.M.S.; Funding Acquisition, D.H.A.F. and D.S.P.; Supervision, D.H.A.F and D.S.P. The authors declare no competing interests. Funding Information: We thank K. Nguyen and K.Y. Lee for technical help in the screens yielding ny10 and fs8 , respectively, and A. Woronik for help with statistical analyses. We thank V. Ambros, G. Ruvkun, T. Montgomery, D. Mathews, S. Bellaousov, A. Mason, A. Samuelson, L. Maquat, D. Moerman, C. Hammel, S. West, and WormBase for constructive discussions and information; F. Slack, V. Ambros, and A. Rougvie for strains; and E. Moss for generously providing the LIN-28 antibody. Some strains were provided by the Caenorhabditis Genetics Center (University of Minnesota), which is funded by the NIH Office of Research Infrastructure Programs ( P40 OD010440 ). This research was supported by NIH R01 GM100140 , NSF DEB 0922012 , NYU RCF 002456 , and research funds from NYU Shanghai (D.H.A.F.) and NIH R01 GM108885 and NSF IOS 1353075 (D.S.P.). E.V. was supported by the University of Rochester Medical Scientist Training Program , NIH T32 GM007356 , and R.A.H. was supported by the New York Consortium for the Advancement of Postdoctoral Scholars, NIH K12 GM102778 . Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = may,
day = "20",
doi = "10.1016/j.devcel.2019.03.003",
language = "English (US)",
volume = "49",
pages = "542--555.e9",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "4",
}