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Program in Molecular Medicine

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Amino Acids, Peptides, and Proteins | Cell Biology | Developmental Biology | Nucleic Acids, Nucleotides, and Nucleosides


Lin28/LIN-28 is a conserved RNA-binding protein that promotes proliferation and pluripotency and can be oncogenic in mammals. Mammalian Lin28 and C. elegans LIN-28 have been shown to inhibit biogenesis of the conserved cellular differentiation-promoting microRNA let-7 by directly binding to unprocessed let-7 transcripts. Lin28/LIN-28 also bind and regulate many mRNAs in diverse cell types. However, the determinants and consequences of LIN-28-mRNA interactions are not well understood. Here, we report that C. elegans LIN-28 represses the expression of LIN-46, a downstream protein in the heterochronic pathway. We find that lin-28 and sequences within the lin-46 5' UTR are required to prevent LIN-46 expression at early larval stages. Moreover, we find that precocious LIN-46 expression caused by mutations in the lin-46 5' UTR is sufficient to cause precocious heterochronic defects similar to those of lin-28(lf) animals. Thus, our findings demonstrate the biological importance of the regulation of individual target mRNAs by LIN-28.


5′ UTR, LIN-28, LIN-46, Lin28, cell fate progression, cell proliferation, heterochronic, let-7, mRNA, pluripotency

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Copyright 2021 The Author(s). This is an open access article under the CC BY-NC-ND license (

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Ilbay O, Nelson C, Ambros V. C. elegans LIN-28 controls temporal cell fate progression by regulating LIN-46 expression via the 5' UTR of lin-46 mRNA. Cell Rep. 2021 Sep 7;36(10):109670. doi: 10.1016/j.celrep.2021.109670. PMID: 34496246; PMCID: PMC8445076. Link to article on publisher's site

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Cell reports

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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.