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Gene regulation

No escape from micromanagement

Nature Reviews Genetics volume 7, pages 82–83 (2006)Cite this article

Using the mouse expression atlas, Farh and Grimson et al. showed that the expression of predicted mRNA targets was lower in tissues in which the corresponding miRNA was expressed. This is not surprising. However, they found that before differentiation and miRNA expression, target mRNA expression was higher. The conclusion from this observation, which is also made by Stark and Brennecke et al., is that miRNAs “dampen the output of preexisting messages to facilitate a more rapid and robust transition to a new expression program.”

A combination of computational prediction and reporter assays revealed that the UTRs of many mRNAs contain potential miRNA binding sites that can mediate miRNA-dependent regulation despite not being evolutionarily conserved. mRNAs that contain these non-conserved sites tend not to be expressed in the tissues in which the corresponding miRNAs are found. Importantly, such sites tend to be underrepresented in genes that are highly expressed in a given tissue and that are involved in basic cellular functions. Genes that 'avoid' having miRNA binding sites have been dubbed 'antitargets' and their existence was proposed in 2004 by Bartel and Chen. Farh and Grimson et al. predict that this effect on the evolution of UTRs is likely to be widespread, influencing the evolution of thousands of UTRs. For some messages that need to be co-expressed with miRNAs, the selection to avoid being targeted is so strong that their UTRs become very short. Stark and Brennecke et al. show that the most abundant among miRNAs targets are developmental genes and that housekeeping genes fall into the antitarget class.

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References

ORIGINAL RESEARCH PAPERS

  1. Kai-How Farh, K. & Grimson, A. et al. The wiedespread impact of mammalian microRNAs on mRNA repression and evolution. Science 310, 1817–1821 (2005)

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  2. Stark, A. & Brennecke, J. et al. Animal microRNAs confer robustness to gene expression and have a significant impact on 3′ UTR evolution. Cell 123, 1133–1146 (2005)

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FURTHER READING

  1. Bartel, D. P. & Chen, C. Z. Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs. Nature Rev. Genet. 5, 396–400 (2004)

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  2. Mattick, J. S. RNA regulation: a new genetics? Nature Rev. Genet. 5, 316–323 (2004)

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

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Authors
  1. Magdalena Skipper
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Skipper, M. No escape from micromanagement. Nat Rev Genet 7, 82–83 (2006). https://doi.org/10.1038/nrg1793

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