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Modulation of miRNA function by natural and synthetic RNA-binding proteins in cancer

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Abstract

RNA-binding proteins (RBPs) and microRNAs (miRNAs) are the most important regulators of mRNA stability and translation in eukaryotic cells; however, the complex interplay between these systems is only now coming to light. RBPs and miRNAs regulate a unique set of targets in either a positive or negative manner and their regulation is mainly opposed to each other on overlapping targets. In some cases, the levels of RBPs or miRNAs regulate the cellular levels of one another and decreased levels of either results in changes in translation of their targets. There is growing evidence that these regulatory circuits are crucial in the development and progression of cancer; however, the rules underlying synergism and antagonism between miRNAs and RNA-binding proteins remain unclear. Synthetic biology seeks to develop artificial systems to better understand their natural counterparts and to develop new, useful technologies for manipulation of gene expression at the RNA level. The recent development of artificial RNA-binding proteins promises to enable a much greater understanding of the importance of the functional interactions between RNA-binding proteins and miRNAs, as well as enabling their manipulation for therapeutic purposes.

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Acknowledgements

Research in our groups has been supported by fellowships, scholarships and grants from the Australian Research Council (FT0991008, FT0991113, DP140104111 to A. F. and O. R.), the National Health and Medical Research Council (APP1058442, APP1045677 to A. F. and O. R.,APP1071081 and APP1084964 to P. L), and the Cancer Council Western Australia (to A. F. and O. R.).

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  1. Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, WA, 6009, Australia

    Pascal D. Vos, Peter J. Leedman, Aleksandra Filipovska & Oliver Rackham

  2. Centre for Medical Research, The University of Western Australia, Nedlands, WA, 6009, Australia

    Pascal D. Vos, Peter J. Leedman & Aleksandra Filipovska

  3. School of Molecular and Chemical Sciences, The University of Western Australia, Crawley, WA, 6009, Australia

    Pascal D. Vos & Aleksandra Filipovska

  4. Medical School, The University of Western Australia, Crawley, WA, 6009, Australia

    Peter J. Leedman

  5. School of Pharmacy and Biomedical Sciences, Curtin University, Bentley, WA, 6102, Australia

    Oliver Rackham

  6. Curtin Health Innovation Research Institute, Curtin University, Bentley, WA, 6102, Australia

    Oliver Rackham

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Vos, P.D., Leedman, P.J., Filipovska, A. et al. Modulation of miRNA function by natural and synthetic RNA-binding proteins in cancer. Cell. Mol. Life Sci. 76, 3745–3752 (2019). https://doi.org/10.1007/s00018-019-03163-9

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