The METHYLTRANSFERASE B–SERRATE interaction mediates the reciprocal regulation of microRNA biogenesis and RNA m6A modification

ABSTRACT In eukaryotes, RNA N 6‐methyladenosine (m6A) modification and microRNA (miRNA)‐mediated RNA silencing represent two critical epigenetic regulatory mechanisms. The m6A methyltransferase complex (MTC) and the microprocessor complex both undergo liquid–liquid phase separation to form nuclear membraneless organelles. Although m6A methyltransferase has been shown to positively regulate miRNA biogenesis, a mechanism of reciprocal regulation between the MTC and the microprocessor complex has remained elusive. Here, we demonstrate that the MTC and the microprocessor complex associate with each other through the METHYLTRANSFERASE B (MTB)–SERRATE (SE) interacting module. Knockdown of MTB impaired miRNA biogenesis by diminishing microprocessor complex binding to primary miRNAs (pri‐miRNAs) and their respective MIRNA loci. Additionally, loss of SE function led to disruptions in transcriptome‐wide m6A modification. Further biochemical assays and fluorescence recovery after photobleaching (FRAP) assay indicated that SE enhances the liquid–liquid phase separation and solubility of the MTC. Moreover, the MTC exhibited enhanced retention on chromatin and diminished binding to its RNA substrates in the se mutant background. Collectively, our results reveal the substantial regulatory interplay between RNA m6A modification and miRNA biogenesis.

• Publication year

  2024

• Venue

  Journal of Integrative Plant Biology

• Publication date

  2024-08-29

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1111/jipb.13770PMID 39206840PMCID 11622539
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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