MLL RIP-seq

We uncovered an unexpected function of mixed-lineage leukemia (MLL) protein, which is a critical epigenetic factor and whose disruption leads to leukemogenesis, in the functional regulation of miRNAs. We reveal that the MLLC180 subunit alone can colocalize with miRNA-induced silencing complex (miRISC) components in cytoplasm processing bodies (P-bodies), where miRNA-mediated gene silencing takes place. In addition, we show that MLL was specifically required for miRNA-mediated translational repression, but not for miRNA or siRNA-mediated mRNA cleavage. Mechanistically, MLL was necessarily required for recruiting miRNA to the miRISC and P-body core, partly through its binding partner RAN. Furthermore, dysregulation of the miRNA repression function in MLL leukemic cells was essential for high-level expression of MYC, which ensured the survival of MLL leukemic cells. Thus, our investigation discovered that the MLL subunit alone can exert other functions in miRNA-mediated gene silencing apart from the epigenetic function of the whole MLL heterodimer. We also demonstrated as proof-of-principle that functional deregulation of miRNA may play an important role in cancer. Overall design: Identify the binding RNAs and small RNAs of the MLL protein using RIP-seq method