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Small RNAs

MicroRNAs get a boost

Nature Reviews Molecular Cell Biology volume 10, pages 302–303 (2009)Cite this article

Schwamborn et al. observed that the TRIM-NHL protein TRIM32 is expressed highly in differentiating mouse neurons. By contrast, they found that TRIM32 is expressed at lower levels in dividing neural progenitor cells, and is segregated asymmetrically between the dividing daughters. Cells in which Trim32 is knocked down retain their neural progenitor status, whereas overexpression of Trim32 in mouse neural progenitors inhibits proliferation and induces differentiation. These data suggest that increased levels of TRIM32 in one of the daughter cells contribute to the decision of this cell to undergo neuronal differentiation.

TRIM32 exerts its effect by ubiquitylating the transcription factor MYC through its amino-terminal RING finger domain, targeting MYC for proteasome-mediated degradation. This results in cell cycle exit and induction of neuronal differentiation. TRIM32 also binds the argonaute 1 (AGO1) protein and enhances the activity of the miRNA let-7a — a known stem cell regulator. Neuronal differentiation is inhibited when let-7a function is blocked, whereas overexpression of let-7a promotes neuronal differentiation. So, TRIM32 uses two mechanisms to modulate proliferation and differentiation in neuronal stem cells.

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References

ORIGINAL RESEARCH PAPERS

  1. Schwamborn, J. C. et al. The TRIM-NHL protein TRIM32 activates microRNAs and prevents self-renewal in mouse neural progenitors. Cell 136, 913–925 (2009)

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  2. Hammell, C. M. et al. nhl-2 modulates microRNA activity in Caenorhabditis elegans. Cell 136, 926–938 (2009)

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FURTHER READING

  1. Eulalio, A. et al. P bodies: at the crossroads of post-transcriptional pathways. Nature Rev. Mol. Cell Biol. 8, 9–22 (2007)

    Article  CAS  Google Scholar 

  2. Hutvagner, G. & Simard, M. J. Argonaute proteins: key players in RNA silencing. Nature Rev. Mol. Cell Biol. 9, 22–32 (2008)

    Article  CAS  Google Scholar 

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Authors
  1. Arianne Heinrichs
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Heinrichs, A. MicroRNAs get a boost. Nat Rev Mol Cell Biol 10, 302–303 (2009). https://doi.org/10.1038/nrm2670

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