title: Makorin ortholog LEP-2 regulates LIN-28 stability to promote the juvenile-to-adult transition in Caenorhabditis elegans.
abstract: The heterochronic genes lin-28, let-7 and lin-41 regulate fundamental developmental transitions in animals, such as stemness versus differentiation and juvenile versus adult states. We identify a new heterochronic gene, lep-2, in Caenorhabditis elegans. Mutations in lep-2 cause a delay in the juvenile-to-adult transition, with adult males retaining pointed, juvenile tail tips, and displaying defective sexual behaviors. In both sexes, lep-2 mutants fail to cease molting or produce an adult cuticle. We find that LEP-2 post-translationally regulates LIN-28 by promoting LIN-28 protein degradation. lep-2 encodes the sole C. elegans ortholog of the Makorin (Mkrn) family of proteins. Like lin-28 and other heterochronic pathway members, vertebrate Mkrns are involved in developmental switches, including the timing of pubertal onset in humans. Based on shared roles, conservation and the interaction between lep-2 and lin-28 shown here, we propose that Mkrns, together with other heterochronic genes, constitute an evolutionarily ancient conserved module regulating switches in development.
authors.affiliation: Department of Biology, New York University, New York, NY 10003, USA.
authors.forename: R Antonio
authors.initials: RA
authors.lastname: Herrera
authors.affiliation: Department of Biology, New York University, New York, NY 10003, USA.
authors.forename: Karin
authors.initials: K
authors.lastname: Kiontke
authors.affiliation: Department of Biology, New York University, New York, NY 10003, USA Faculty of Arts and Sciences, New York University-Shanghai, Shanghai 200122, China david.fitch@nyu.edu.
authors.forename: David H A
authors.initials: DH
authors.lastname: Fitch
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D002874:Chromosome Mapping; D055028:Comparative Genomic Hybridization; D004843:Epistasis, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005816:Genetic Complementation Test; D008297:Male; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D010641:Phenotype; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional; D012097:Repressor Proteins / Q000502:physiology*; D012261:Ribonucleoproteins / Q000235:genetics / Q000502:physiology*; D019076:Transgenes
chemical_list: D029742:Caenorhabditis elegans Proteins; C000609485:LEP-2 protein, C elegans; C452195:LIN-28 protein, C elegans; D012097:Repressor Proteins; D012261:Ribonucleoproteins
keywords: Developmental timing; Heterochronic pathway; LIN-28/let-7 axis; Mkrn
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