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Many roads to maturity: microRNA biogenesis pathways and their regulation

Abstract

MicroRNAs are important regulators of gene expression that control both physiological and pathological processes such as development and cancer. Although their mode of action has attracted great attention, the principles governing their expression and activity are only beginning to emerge. Recent studies have introduced a paradigm shift in our understanding of the microRNA biogenesis pathway, which was previously believed to be universal to all microRNAs. Maturation steps specific to individual microRNAs have been uncovered, and these offer a plethora of regulatory options after transcription with multiple proteins affecting microRNA processing efficiency. Here we review the recent advances in knowledge of the microRNA biosynthesis pathways and discuss their impact on post-transcriptional microRNA regulation during tumour development.

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Figure 1: The 'linear' canonical pathway of microRNA processing.
Figure 2: Regulation of pri-miRNA processing.
Figure 3: Lin-28 inhibits let-7 biogenesis.
Figure 4: Regulation of microRNA processing factors.
Figure 5: Ago2 generates an additional intermediate, the ac-pre-miRNA.

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Acknowledgements

We apologize to all scientists whose work could not be cited in this review as a result of space constraints. Research in the Diederichs laboratory is funded by grants from the Helmholtz Society (VH-NG-504), the German Cancer Research Center DKFZ, the Institute of Pathology, University of Heidelberg, and the Marie Curie Programme of the European Commission. Research in the Gregory laboratory is supported by the Children's Hospital, Boston, the Harvard Stem Cell Institute, the March of Dimes Basil O'Conner award, the Charles H. Hood Foundation, and the Emerald Foundation. R.I.G. is a Pew Research Scholar.

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Winter, J., Jung, S., Keller, S. et al. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 11, 228–234 (2009). https://doi.org/10.1038/ncb0309-228

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