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Tumorigenesis

Micromanager

Nature Reviews Molecular Cell Biology volume 6, pages 360–361 (2005)Cite this article

Animal miRNAs are proposed to exert their regulatory effects by binding to complementary sequences in the 3′ untranslated regions (UTRs) of their target mRNA, thereby controlling translation. One of the first miRNAs to be discovered was let-7 in the worm Caenorhabditis elegans, and there are now four let-7 relatives known in these creatures. let-7 controls cell fate in hypodermal seam cells, which are a type of epithelial cell, but the functions of the other family members are unknown. Johnson et al. searched the C. elegans genome for potential target genes, looking for sites complementary to a consensus let-7 family sequence in the 3′ UTRs of genes. The highest-scoring candidate was let-60, the C. elegans homologue of human RAS.

The authors found that let-7 and let-60 were both expressed in hypodermal seam cells, but in a reciprocal manner, so that during developmental stages when let-7 was high, let-60 was low, and vice versa. Moreover, the let-60 3′ UTR was sufficient to downregulate a reporter gene at the developmental stage when let-60 expression normally drops off. Notably, in worms with let-7 loss-of-function mutations, there was no decline in reporter-gene expression. All of which indicates that the let-60 mRNA is a functional target of let-7 in worms.

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References

ORIGINAL RESEARCH PAPER

  1. Johnson, S. M. et al. RAS is regulated by the let-7 microRNA family. Cell 120, 635–647 (2005)

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FURTHER READING

  1. Downward, J. Targeting RAS signalling pathways in cancer therapy. Nature Rev. Cancer 3, 11–22 (2003)

    Article  CAS  Google Scholar 

  2. He, L. & Hannon, G. J. MicroRNAs: small RNAs with a big role in gene regulation. Nature Rev. Genet. 5, 522–531 (2004)

    Article  CAS  Google Scholar 

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  1. Nature Reviews Cancer,

    Helen Dell

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  1. Helen Dell
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Dell, H. Micromanager. Nat Rev Mol Cell Biol 6, 360–361 (2005). https://doi.org/10.1038/nrm1653

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