TY - JOUR TI - Aven recognition of RNA G-quadruplexes regulates translation of the mixed lineage leukemia protooncogenes AU - Thandapani, Palaniraja AU - Song, Jingwen AU - Gandin, Valentina AU - Cai, Yutian AU - Rouleau, Samuel G AU - Garant, Jean-Michel AU - Boisvert, Francois-Michel AU - Yu, Zhenbao AU - Perreault, Jean-Pierre AU - Topisirovic, Ivan AU - Richard, Stéphane A2 - Green, Rachel VL - 4 PY - 2015 DA - 2015/08/12 SP - e06234 C1 - eLife 2015;4:e06234 DO - 10.7554/eLife.06234 UR - https://doi.org/10.7554/eLife.06234 AB - 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. KW - G-quadruplex KW - arginine methylation KW - PRMT1 KW - RNA-binding protein KW - translation JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -