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Small RNAs

Bound to silence

Nature Reviews Molecular Cell Biology volume 10, page 579 (2009)Cite this article

Gruber et al. knocked down ARS2 by RNA interference in mammalian cells and observed defects in proliferation. Furthermore, knockout of Ars2 in adult mouse haematopoietic tissues (which are highly proliferative) causes bone marrow defects, whereas the liver and kidney (which comprise mainly non-proliferating cells) are unaffected. The authors identified nuclear cap-binding protein 1 (NCBP1; also known as CBP80), which assembles on 7mG-capped RNAs, in a screen for ARS2-interacting proteins and showed that ARS2 also interacts with NCBP2 (also known as CBP20) and 7mG-capped RNAs in vitro.

Genetic studies in plants previously showed that SERRATE (the homologue of ARS2) is involved in miRNA biogenesis, and plants deficient in SERRATE have similar defects to those observed in CBC mutants. In agreement with these observations, Gruber et al. showed that knockdown of ARS2 or CBP80 in proliferating mammalian cells reduces the levels of a subset of miRNAs that have been implicated in cellular transformation (for example, let-7) and disrupts let-7 miRNA-mediated repression of a reporter transcript. Furthermore, ARS2 binds to and stimulates the activity and fidelity of Drosha, a component of the Microprocessor complex that cleaves primary miRNA transcripts (pri-miRNAs) in the nucleus to generate pre-miRNAs. By contrast, ARS2 does not bind to Dicer, which processes pre-miRNAs to generate mature miRNAs in the cytoplasm. Notably, ARS2 is selectively expressed in proliferating cells, which suggests that processing of a subset of pri-miRNAs correlates with proliferation.

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References

ORIGINAL RESEARCH PAPERS

  1. Gruber, J. J. et al. Ars2 links the nuclear cap-binding complex to RNA interference and cell proliferation. Cell 138, 328–339 (2009)

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  2. Sabin, L. R. et al. Ars2 regulates both miRNA- and siRNA-dependent silencing and suppresses RNA virus infection in Drosophila. Cell 138, 340–351 (2009)

    Article  CAS  Google Scholar 

FURTHER READING

  1. Kim, V. N. et al. Biogenesis of small RNAs in animals. Nature Rev. Mol. Cell Biol. 10, 126–139 (2009)

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Authors
  1. Francesca Cesari
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Cesari, F. Bound to silence. Nat Rev Mol Cell Biol 10, 579 (2009). https://doi.org/10.1038/nrm2754

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