METTL1 Promotes let-7 MicroRNA Processing via m7G Methylation

Mol Cell. 2019 Jun 20;74(6):1278-1290.e9. doi: 10.1016/j.molcel.2019.03.040. Epub 2019 Apr 25.


7-methylguanosine (m7G) is present at mRNA caps and at defined internal positions within tRNAs and rRNAs. However, its detection within low-abundance mRNAs and microRNAs (miRNAs) has been hampered by a lack of sensitive detection strategies. Here, we adapt a chemical reactivity assay to detect internal m7G in miRNAs. Using this technique (Borohydride Reduction sequencing [BoRed-seq]) alongside RNA immunoprecipitation, we identify m7G within a subset of miRNAs that inhibit cell migration. We show that the METTL1 methyltransferase mediates m7G methylation within miRNAs and that this enzyme regulates cell migration via its catalytic activity. Using refined mass spectrometry methods, we map m7G to a single guanosine within the let-7e-5p miRNA. We show that METTL1-mediated methylation augments let-7 miRNA processing by disrupting an inhibitory secondary structure within the primary miRNA transcript (pri-miRNA). These results identify METTL1-dependent N7-methylation of guanosine as a new RNA modification pathway that regulates miRNA structure, biogenesis, and cell migration.

Keywords: 7-methylguanosine; G-quadruplexes; METTL1; RNA methylation; SAM-dependent methyltransferase; cell migration; high-throughput sequencing; let-7; miRNA biogenesis; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Base Sequence
  • Biological Assay
  • Caco-2 Cells
  • Cell Movement
  • Cell Proliferation
  • Guanosine / analogs & derivatives*
  • Guanosine / metabolism
  • HEK293 Cells
  • Humans
  • Methylation
  • Methyltransferases / genetics*
  • Methyltransferases / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Nucleic Acid Conformation
  • RNA Processing, Post-Transcriptional*


  • MicroRNAs
  • mirnlet7 microRNA, human
  • Guanosine
  • 7-methylguanosine
  • METTL1 protein, human
  • Methyltransferases