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Elife. 2015 Aug 12;4. doi: 10.7554/eLife.06234.

Aven recognition of RNA G-quadruplexes regulates translation of the mixed lineage leukemia protooncogenes.

Author information

1
Terry Fox Molecular Oncology Group, Segal Cancer Center, Jewish General Hospital, Montréal, Canada.
2
Département de Biochimie, Université de Sherbrooke, Sherbrooke, Canada.
3
Département d'Anatomie et de Biologie Cellulaire, Faculté de Médecine et des Sciences de la Santé, Pavillon de Recherche Appliquée au Cancer, Université de Sherbrooke, Sherbrooke, 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 resulting 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.

KEYWORDS:

G-quadruplex; PRMT1; RNA-binding protein; arginine methylation; biochemistry; cell biology; human; mouse; translation

PMID:
26267306
PMCID:
PMC4561382
DOI:
10.7554/eLife.06234
[Indexed for MEDLINE]
Free PMC Article

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