Makorin ortholog LEP-2 regulates LIN-28 stability to promote the juvenile-to-adult transition in Caenorhabditis elegans

• Published in: Development (Cambridge) Vol. 143; no. 5; pp. 799 - 809
• Main Authors: Herrera, R Antonio, Kiontke, Karin, Fitch, David H A
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 01.03.2016
• Subjects: Alleles; Amino Acid Sequence; Animals; Caenorhabditis elegans - genetics; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - physiology; Cell Differentiation; Chromosome Mapping; Comparative Genomic Hybridization; Epistasis, Genetic; Female; Gene Expression Regulation, Developmental; Genetic Complementation Test; Male; Molecular Sequence Data; Mutagenesis; Mutation; Phenotype; Repressor Proteins - physiology; Ribonucleoproteins - genetics; Ribonucleoproteins - physiology; RNA Interference; RNA Processing, Post-Transcriptional; Transgenes; Heterochronic pathway; LIN-28/let-7 axis; Developmental timing; Mkrn
• ISSN: 0950-1991; 1477-9129
• DOI: 10.1242/dev.132738

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.