Abstract
MicroRNAs (miRNAs) are pivotal regulators involved in various biological functions through the post-transcriptional regulation of gene expression. Alterations of miRNA expression and function contribute to both physiological and pathological processes such as development and cancer. While their roles have been attracting more attention in connection with tumor development, the mechanisms regulating miRNA biogenesis have not been well understood. Accumulating evidences have revealed the dynamic regulation of miRNA biosynthesis by several regulatory factors and demonstrated the complexity of miRNA-mediated gene regulation. In addition, several reports showed the interplay between the p53 tumor suppressor network and the miRNA-mediated gene regulatory system. We recently found that p53 modulates miRNA maturation at the processing step of primary miRNA transcripts, unraveling a novel function of p53. Here, we review the recent understanding of functional links between miRNA biogenesis and intracellular signaling pathways, with particular focus on the crosstalk between the p53 network and the miRNA biogenesis machinery. Further characterization of controlling elements for miRNA production and activity would provide important insights for a comprehensive understanding of the miRNA function in health and disease.
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Acknowledgments
We apologize to all scientists whose work could not be cited in this review as a result of space constraints. We thank the members of Department of Molecular Pathology, University of Tokyo. This work was supported by KAKENHI (Grant-in-Aid for Scientific Research) and Global Center of Excellence Program for “Integrative Life Science Based on the Study of Biosignaling Mechanisms” from the Ministry of Education, Culture, Sports, Science and Technology of Japan. H.I.S. is supported by a research fellowship of the Japan Society for the Promotion of Science for Young Scientists.
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Suzuki, H.I., Miyazono, K. Dynamics of microRNA biogenesis: crosstalk between p53 network and microRNA processing pathway. J Mol Med 88, 1085–1094 (2010). https://doi.org/10.1007/s00109-010-0650-1
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DOI: https://doi.org/10.1007/s00109-010-0650-1