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PRMT1-mediated methylation of the microprocessor-associated proteins regulates microRNA biogenesis

Valeria Spadotto1, Roberto Giambruno1, Enrico Massignani1

  • 1Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy.

Nucleic Acids Research
|November 29, 2019
PubMed

Insights

Microprocessor complex methylation regulates microRNA (miRNA) biogenesis. Protein arginine methyltransferases (PRMTs) control methylation, impacting pri-to-pre-miRNA processing and global miRNA expression.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Epigenetics

Background:

  • MicroRNA (miRNA) biogenesis is a crucial nuclear process involving the Microprocessor complex.
  • Regulation of miRNA production is essential for cellular function and gene expression control.

Purpose of the Study:

  • To investigate the role of post-translational modifications, specifically methylation, in Microprocessor complex function.
  • To identify methylated sites within the Microprocessor complex and their impact on miRNA biogenesis.

Main Methods:

  • High-resolution mass spectrometry (MS)-proteomics to identify methylated sites.
  • Depletion and pharmacological inhibition of Type-I Protein Arginine Methyltransferases (PRMTs).
  • Analysis of pri-to-pre-miRNA processing and miRNA expression levels.

Main Results:

  • Identified 84 methylated sites on 19 of 24 Microprocessor subunits, predominantly arginine methylation.
  • PRMTs inhibition led to altered methylation states and decreased global miRNA expression.
  • Reduced ILF3 methylation impaired its binding to specific pri-miRNAs, affecting processing.

Conclusions:

  • Arginine methylation is a key regulatory mechanism in mammalian miRNA biogenesis.
  • PRMTs and Microprocessor complex methylation are critical for efficient pri-to-pre-miRNA processing.
  • This study uncovers a novel epigenetic layer controlling miRNA production.

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