@article{2c8a76fe0b4f4618a35f2f2adecbc99f,
title = "The makorin lep-2 and the lncrna lep-5 regulate lin-28 to schedule sexual maturation of the c. Elegans nervous system",
abstract = "Sexual maturation must occur on a controlled developmental schedule. In mammals, Makorin3 (MKRN3) and the miRNA regulators LIN28A/B are key regulators of this process, but how they act is unclear. In C. elegans, sexual maturation of the nervous system includes the functional remodeling of postmitotic neurons and the onset of adult-specific behaviors. Here, we find that the lin-28-let-7 axis (the {\textquoteleft}heterochronic pathway{\textquoteright}) determines the timing of these events. Upstream of lin-28, the Makorin lep-2 and the lncRNA lep-5 regulate maturation cell-autonomously, indicating that distributed clocks, not a central timer, coordinate sexual differentiation of the C. elegans nervous system. Overexpression of human MKRN3 delays aspects of C. elegans sexual maturation, suggesting the conservation of Makorin function. These studies reveal roles for a Makorin and a lncRNA in timing of sexual differentiation; moreover, they demonstrate deep conservation of the lin-28-let-7 system in controlling the functional maturation of the nervous system.",
author = "Hannah Lawson and Edward Vuong and Miller, {Renee M.} and Karin Kiontke and Fitch, {David Ha} and Portman, {Douglas S.}",
note = "Funding Information: National Institute of General Medical SciencesR01 GM108885, Douglas Portman National Institute of General Medical SciencesR01 GM130136, Douglas Portman National Science Foundation IOS1353075, Douglas Portman National Institute of General Medical SciencesT32 GM007356, Edward Vuong National Institute of General Medical SciencesR01 GM100140, David Fitch National Science FoundationDEB 0922012, David Fitch New York University David Fitch Funding Information: We are grateful to Jintao Luo for help with strain construction, Victoria DiMarco and Adam Mason for preliminary studies on srj-54, Laura Pereira and Oliver Hobert for sharing unpublished results, and Florian Aeschimann and Helge Gro{\ss}hans for providing lin-29a alleles. Some strains used in this work 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 GM108885, R01 GM130136, and NSF IOS 1353075 (to DSP) and by NIH R01 GM100140, NSF DEB 0922012, and research funds from NYU Shanghai (to DHAF). EV was supported by the University of Rochester Medical Scientist Training Program, NIH T32 GM007356. Publisher Copyright: {\textcopyright} Lawson et al.",
year = "2019",
doi = "10.7554/elife.43660",
language = "English (US)",
volume = "8",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}