m7G methylation by METTL1 regulates let-7 microRNAs [Expression Microarray KD A549]

Methylation of N7-methylguanosine (m7G) is found at mRNA caps and at defined internal positions within abundant tRNAs and rRNAs. However, its detection within low abundance mRNAs and microRNAs (miRNAs) has been hampered by lack of sensitive detection strategies. Here, we adapt a chemical reactivity assay to detect internal m7G in RNA from eukaryotic cells. Using this approach, alongside a confirmational RNA immunoprecipitation assay, we identify m7G within miRNAs inhibiting cell migration, and show that METTL1 mediates this m7G methylation. Using Let-7 as an example we demonstrate that METTL1 activity is necessary for correct processing, is required for Let-7 dependent gene regulation and consequently has a negative effect on cell migration. These results identify m7G modification as a new pathway for the regulation of miRNAs. Microarray global gene expression analysis to identify transcripts affected by depletion of METTL1 in human A549 cells