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Effects on prostate cancer cells of targeting RNA polymerase III

Petrie, John L; Swan, Caroline; Ingram, Richard M; Frame, Fiona M; Collins, Anne T; Dumay-Odelot, Hélène; Teichmann, Martin; Maitland, Norman J; White, Robert J

Authors

John L Petrie

Caroline Swan

Richard M Ingram

Anne T Collins

Hélène Dumay-Odelot

Martin Teichmann

Norman J Maitland

Robert J White



Contributors

Abstract

RNA polymerase (pol) III occurs in two forms, containing either the POLR3G subunit or the related paralogue POLR3GL. Whereas POLR3GL is ubiquitous, POLR3G is enriched in undifferentiated cells. Depletion of POLR3G selectively triggers proliferative arrest and differentiation of prostate cancer cells, responses not elicited when POLR3GL is depleted. A small molecule pol III inhibitor can cause POLR3G depletion, induce similar differentiation and suppress proliferation and viability of cancer cells. This response involves control of the fate-determining factor NANOG by small RNAs derived from Alu short interspersed nuclear elements. Tumour initiating activity in vivo can be reduced by transient exposure to the pol III inhibitor. Untransformed prostate cells appear less sensitive than cancer cells to pol III depletion or inhibition, raising the possibility of a therapeutic window.

Journal Article Type Article
Publication Date May 7, 2019
Journal Nucleic Acids Research
Print ISSN 0305-1048
Electronic ISSN 1362-4962
Publisher Oxford University Press (OUP)
Peer Reviewed Peer Reviewed
Volume 47
Issue 8
Pages 3937-3956
Institution Citation Petrie, J. L., Swan, C., Ingram, R. M., Frame, F. M., Collins, A. T., Dumay-Odelot, H., …White, R. J. (2019). Effects on prostate cancer cells of targeting RNA polymerase III. Nucleic Acids Research, 47(8), 3937-3956. https://doi.org/10.1093/nar/gkz128
DOI https://doi.org/10.1093/nar/gkz128
Keywords Genetics
Publisher URL https://academic.oup.com/nar/article/47/8/3937/5367413

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Copyright Statement
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.



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