Fig. 4
Post-transcriptional gene expression regulation by RBPs directly assessed in MLL-r leukemia. METTL3 and METTL14 function as m6A writers, FTO and ALKBH5 function as m6A erasers, and YTHDF2 functions as an m6A reader. ADAR1 catalyzes A-to-I RNA editing. RBPs involved in alternative splicing include the trans-acting splicing factor RBM39, the 5′ cap binding enzyme DCPS, and MBNL1. NCL has been shown to bind to the 3′UTR of mRNA transcripts and be required for miR biogenesis. ZFP36L1 binds to the 3′UTR of mRNA transcripts such as CDK6. DROSHA has been implicated to be recruited by MLL-AF4 and MLL-AF9 to target genes encoding miRs as well as function in the cytoplasm in non-canonical miR biogenesis. The METTL1/WDR4 heterodimeric complex catalyzes m7G modifications on tRNA. Multifunctional RBPs: LIN28B localizes in P-bodies, stress granules, and mRNP complexes and has an important function in miR biogenesis. MSI2 has been shown to bind to the 3′UTR of mRNA transcripts and interact with SYNCRIP to target the same transcripts. MSI2 may also have a function in alternative splicing. IGF2BP3 has been shown to function in alternative splicing, RNA modifications as an m6A reader, localization within ribonucleoprotein complexes (RNPs) and stress granules, and binding to the 3′ untranslated region (3′UTR) of mRNA transcripts impacting their association with the RNA induced silencing complex (RISC) to regulate the stability, translation, and degradation of target transcripts