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Small RNAs

Controlling maturity

Nature Reviews Molecular Cell Biology volume 13, pages 752–753 (2012)Cite this article

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While carrying out a screen to identify previously uncharacterized methyltransferases, Xhemalce et al. identified BCDIN3D, an enzyme that targets 5′ monophosphate. As this feature is found in both pre-miRNAs and mature miRNAs, the authors asked whether BCDIN3D has a role in miRNA biogenesis. Indeed, they showed that the levels of five miRNAs, including miR-145, significantly increased upon BCDIN3D depletion. Interestingly, although pri-miR-145 levels were unchanged, pre-miR-145 levels significantly decreased after BCDIN3D depletion, and this correlated with reduced levels of the miR-145 target insulin receptor substrate 1 (IRS1). This suggests that BCDIN3D exerts its effects during miRNA biogenesis rather than during pri-miRNA transcription. Indeed, BCDIN3D was found to dimethylate the 5′ monophosphate end of pre-miR-145 both in vitro and in cells. Moreover, this modification inhibited processing of pre-miR-145 by Dicer, indicating that methylation of pre-miRNAs can negatively regulate miRNA biogenesis.

The maturation of another class of miRNAs, let-7, is also negatively regulated by a post-transcriptional modification. In this case, terminal uridylyl transferases (TUTs) are recruited to the pre-miRNA by LIN28 and generate a long single-stranded tail of Us (known as oligo-uridylation) at the 3′ end of the precursor, thereby blocking further processing by Dicer. Thornton et al. show that the C2H2 zinc-finger domain of TUT4 is essential for its interaction with LIN28 and the consequent oligo-uridylation of pre-let-7 in vitro. This domain is conserved in TUT7, which the authors find can also oligo-uridylate pre-let-7 in embryonic stem cells and has a combinatorial effect with TUT4.

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ORIGINAL RESEARCH PAPERS

  1. Xhemalce, B., Robson, S. C. & Kouzarides, T. Human RNA methyltransferase BCDIN3D regulates microRNA processing. Cell 151, 278–288 (2012)

    Article  CAS  Google Scholar 

  2. Thornton, J. E. et al. Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7). RNA 18, 1875–1885 (2012)

    Article  CAS  Google Scholar 

  3. Heo, I. et al. Mono-uridylation of pre-microRNA as a key step in the biogenesis of group II let-7 microRNAs. Cell 11 Oct 2012 (doi:10.1016/j.cell.2012.09.022)

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  1. Rachel David
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David, R. Controlling maturity. Nat Rev Mol Cell Biol 13, 752–753 (2012). https://doi.org/10.1038/nrm3475

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  • DOI: https://doi.org/10.1038/nrm3475

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