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RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer

(2014) NATURE. 513(7516). p.65-70
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Abstract
The translational control of oncoprotein expression is implicated in many cancers. Here we report an eIF4A RNA helicase-dependent mechanism of translational control that contributes to oncogenesis and underlies the anticancer effects of silvestrol and related compounds. For example, eIF4A promotes T-cell acute lymphoblastic leukaemia development in vivo and is required for leukaemia maintenance. Accordingly, inhibition of eIF4A with silvestrol has powerful therapeutic effects against murine and human leukaemic cells in vitro and in vivo. We use transcriptome-scale ribosome footprinting to identify the hallmarks of eIF4A-dependent transcripts. These include 5' untranslated region (UTR) sequences such as the 12-nucleotide guanine quartet (CGG)(4) motif that can form RNA G-quadruplex structures. Notably, among the most eIF4A-dependent and silvestrol-sensitive transcripts are a number of oncogenes, superenhancer-associated transcription factors, and epigenetic regulators. Hence, the 5' UTRs of select cancer genes harbour a targetable requirement for the eIF4A RNA helicase.
Keywords
C-MYC, EIF4E, INITIATION, OF-FUNCTION MUTATIONS, ACUTE LYMPHOBLASTIC-LEUKEMIA, AKT, MOTIF, INHIBITION, TRANSCRIPTION, CAP

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Chicago
Wolfe, Andrew L, Kamini Singh, Yi Zhong, Philipp Drewe, Vinagolu K Rajasekhar, Viraj R Sanghvi, Konstantinos J Mavrakis, et al. 2014. “RNA G-quadruplexes Cause eIF4A-dependent Oncogene Translation in Cancer.” Nature 513 (7516): 65–70.
APA
Wolfe, A. L., Singh, K., Zhong, Y., Drewe, P., Rajasekhar, V. K., Sanghvi, V. R., Mavrakis, K. J., et al. (2014). RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer. NATURE, 513(7516), 65–70.
Vancouver
1.
Wolfe AL, Singh K, Zhong Y, Drewe P, Rajasekhar VK, Sanghvi VR, et al. RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer. NATURE. 2014;513(7516):65–70.
MLA
Wolfe, Andrew L, Kamini Singh, Yi Zhong, et al. “RNA G-quadruplexes Cause eIF4A-dependent Oncogene Translation in Cancer.” NATURE 513.7516 (2014): 65–70. Print.
@article{5822949,
  abstract     = {The translational control of oncoprotein expression is implicated in many cancers. Here we report an eIF4A RNA helicase-dependent mechanism of translational control that contributes to oncogenesis and underlies the anticancer effects of silvestrol and related compounds. For example, eIF4A promotes T-cell acute lymphoblastic leukaemia development in vivo and is required for leukaemia maintenance. Accordingly, inhibition of eIF4A with silvestrol has powerful therapeutic effects against murine and human leukaemic cells in vitro and in vivo. We use transcriptome-scale ribosome footprinting to identify the hallmarks of eIF4A-dependent transcripts. These include 5' untranslated region (UTR) sequences such as the 12-nucleotide guanine quartet (CGG)(4) motif that can form RNA G-quadruplex structures. Notably, among the most eIF4A-dependent and silvestrol-sensitive transcripts are a number of oncogenes, superenhancer-associated transcription factors, and epigenetic regulators. Hence, the 5' UTRs of select cancer genes harbour a targetable requirement for the eIF4A RNA helicase.},
  author       = {Wolfe, Andrew L and Singh, Kamini and Zhong, Yi and Drewe, Philipp and Rajasekhar, Vinagolu K and Sanghvi, Viraj R and Mavrakis, Konstantinos J and Jiang, Man and Roderick, Justine E and Van der Meulen, Joni and Schatz, Jonathan H and Rodrigo, Christina M and Zhao, Chunying and Rondou, Pieter and de Stanchina, Elisa and Teruya-Feldstein, Julie and Kelliher, Michelle A and Speleman, Franki and Porco, John A, Jr and Pelletier, Jerry and Rätsch, Gunnar and Wendel, Hans-Guido},
  issn         = {0028-0836},
  journal      = {NATURE},
  keywords     = {C-MYC,EIF4E,INITIATION,OF-FUNCTION MUTATIONS,ACUTE LYMPHOBLASTIC-LEUKEMIA,AKT,MOTIF,INHIBITION,TRANSCRIPTION,CAP},
  language     = {eng},
  number       = {7516},
  pages        = {65--70},
  title        = {RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer},
  url          = {http://dx.doi.org/10.1038/nature13485},
  volume       = {513},
  year         = {2014},
}

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