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Program in Molecular Medicine

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Developmental Biology | Genetics and Genomics | Nucleic Acids, Nucleotides, and Nucleosides


The let-7 gene encodes a highly conserved microRNA with critical functions integral to cell fate specification and developmental progression in diverse animals. In Caenorhabditis elegans, let-7 is a component of the heterochronic (developmental timing) gene regulatory network, and loss-of-function mutations of let-7 result in lethality during the larval to adult transition due to misregulation of the conserved let-7 target, lin-41. To date, no bilaterian animal lacking let-7 has been characterized. In this study, we identify a cohort of nematode species within the genus Caenorhabditis, closely related to C. elegans, that lack the let-7 microRNA, owing to absence of the let-7 gene. Using Caenorhabditis sulstoni as a representative let-7-lacking species to characterize normal larval development in the absence of let-7, we demonstrate that, except for the lack of let-7, the heterochronic gene network is otherwise functionally conserved. We also report that species lacking let-7 contain a group of divergent let-7 paralogs-also known as the let-7-family of microRNAs-that have apparently assumed the role of targeting the LIN-41 mRNA.


Caenorhabditis elegans, Caenorhabditis macrosperma, Caenorhabditis sulstoni, Elegans group, Elegans supergroup, Japonica group, let-7 microRNA

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Copyright © The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (, which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact

DOI of Published Version



Nelson C, Ambros V. A cohort of Caenorhabditis species lacking the highly conserved let-7 microRNA. G3 (Bethesda). 2021 Apr 23;11(3):jkab022. doi: 10.1093/g3journal/jkab022. PMID: 33890616; PMCID: PMC8063082. Link to article on publisher's site

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G3 (Bethesda, Md.)

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Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.