Aven recognition of RNA G-quadruplexes regulates translation of the mixed lineage leukemia protooncogenes
- Jewish General Hospital, Canada
- Université de Sherbrooke, Canada
- McGill University, Canada
Abstract
G-quadruplexes (G4) are extremely stable secondary structures forming stacks of guanine tetrads. DNA G4 structures have been extensively studied, however, less is known about G4 motifs in mRNAs, especially in their coding sequences. Herein, we show that Aven stimulates the mRNA translation of the mixed lineage leukemia (MLL) proto-oncogene in an arginine methylation-dependent manner. The Aven RGG/RG motif bound G4 structures within the coding regions of the MLL1 and MLL4 mRNAs increasing their polysomal association and translation, resulting in the induction of transcription of leukemic genes. The DHX36 RNA helicase associated with the Aven complex and was required for optimal translation of G4 mRNAs. Depletion of Aven led to a decrease in synthesis of MLL1 and MLL4 proteins esulting in reduced proliferation of leukemic cells. These findings identify an Aven-centered complex that stimulates the translation of G4 harboring mRNAs, thereby promoting survival of leukemic cells.
Article and author information
Author details
Reviewing Editor
- Rachel Green, Johns Hopkins School of Medicine, United States
Version history
- Received: December 23, 2014
- Accepted: August 11, 2015
- Accepted Manuscript published: August 12, 2015 (version 1)
- Version of Record published: September 8, 2015 (version 2)
Copyright
© 2015, Thandapani et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Aven recognition of RNA G-quadruplexes regulates translation of the mixed lineage leukemia protooncogenes
eLife 4:e06234.
https://doi.org/10.7554/eLife.06234
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