Aven recognition of RNA G - quadruplexes regulates 2 translation of the Mixed Lineage Leukemia protooncogenes
نویسندگان
چکیده
25 G-quadruplexes (G4) are extremely stable secondary structures forming stacks of guanine 26 tetrads. DNA G4 structures have been extensively studied, however, less is known about G4 27 motifs in mRNAs, especially in their coding sequences. Herein, we show that Aven stimulates 28 the mRNA translation of the mixed lineage leukemia (MLL) proto-oncogene in an arginine 29 methylation-dependent manner. The Aven RGG/RG motif bound G4 structures within the coding 30 regions of the MLL1 and MLL4 mRNAs increasing their polysomal association and translation, 31 resulting in the induction of transcription of leukemic genes. The DHX36 RNA helicase 32 associated with the Aven complex and was required for optimal translation of G4 mRNAs. 33 Depletion of Aven led to a decrease in synthesis of MLL1 and MLL4 proteins resulting in 34 reduced proliferation of leukemic cells. These findings identify an Aven-centered complex that 35 stimulates the translation of G4 harboring mRNAs, thereby promoting survival of leukemic cells. 36
منابع مشابه
Aven recognition of RNA G-quadruplexes regulates translation of the mixed lineage leukemia protooncogenes
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 R...
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