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mRNA decay

Removing the tail

Nature Reviews Molecular Cell Biology volume 10, pages 736–737 (2009)Cite this article

To explore how miRNAs induce mRNA silencing by removing the poly(A) tail, the authors carried out their experiments in extracts from mouse Krebs 2 ascites cells, which contain let-7 miRNA and have been shown to inhibit mRNA translation. Incubation of mRNA with Krebs 2 extracts resulted in the formation of a new mRNA species, shown to be a deadenylated form of the original mRNA. The generation of the deadenylated mRNA species depended on let-7, as addition of an antisense oligonucleotide complementary to the let-7 miRNA abrogated this response. Inhibition of translation initiation or elongation in Krebs 2 extracts did not interfere with mRNA deadenylation, suggesting that the two silencing mechanisms operate independently. Translation was also partially repressed before detectable deadenylation, suggesting that the two mechanisms act cooperatively but in a temporal manner.

Next, the authors sought to identify the proteins that are involved in miRNA-mediated mRNA deadenylation. miRNAs interact with Argonaute (Ago) proteins to form the RNA-induced silencing complex (RISC), so they searched for proteins that interact with AGO1 (also known as EIF2C1) and AGO2 (also known as EIF2C2). They isolated CAF1 and PABP; CAF1 had not been reported previously to interact with Ago proteins in mammals. Interestingly, depletion of CAF1 from Krebs 2 extracts decreased deadenylation levels and partially relieved the inhibition on mRNA translation. This finding confirms that CAF1, at least in part, mediates mRNA deadenylation. A similar effect on deadenylation was observed with PABP depletion from Krebs 2 extracts, suggesting that PABP also has a role in this process.

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References

ORIGINAL RESEARCH PAPER

  1. Fabian, M. R. et al. Mammalian miRNA RISC recruits CAF1 and PABP to affect PABP-dependent deadenylation. Mol. Cell 27 Aug 2009 (doi:10.1016/j.molcel.2009.08.004)

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FURTHER READING

  1. Goldstrohm, A. C. & Wickens, M. Multifunctional deadenylase complexes diversify mRNA control. Nature Rev. Mol. Cell Biol. 9, 337–344 (2008)

    Article  CAS  Google Scholar 

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Authors
  1. Rachel David
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David, R. Removing the tail. Nat Rev Mol Cell Biol 10, 736–737 (2009). https://doi.org/10.1038/nrm2781

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  • DOI: https://doi.org/10.1038/nrm2781

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