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Coilin mediates m6A RNA methylation through phosphorylation of METTL3

Douglas M McLaurin1, Sara K Tucker1, Michael D Hebert1

  • 1Department of Cell and Molecular Biology, The University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.

Biology Open
|December 5, 2023
PubMed

Insights

The protein coilin plays a role in microRNA (miRNA) biogenesis by influencing m6A RNA methylation. Coiln suppression affects key proteins involved in this process, revealing a novel regulatory mechanism.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • RNA Biology

Background:

  • MicroRNAs (miRNAs) are crucial regulators of gene expression.
  • miRNA biogenesis involves processing of primary miRNAs by the microprocessor complex.
  • m6A RNA methylation, mediated by METTL3 and hnRNPA2B1, is a key regulatory step in miRNA biogenesis.

Purpose of the Study:

  • To investigate the potential role of coilin in miRNA biogenesis.
  • To determine if coilin influences m6A RNA methylation during miRNA processing.

Main Methods:

  • Coilin suppression using specific techniques.
  • Assessing m6A levels on primary miRNAs (Let7a and miR-21).
  • Analyzing protein expression of hnRNPA2B1 and METTL3.
  • Investigating the interaction between coilin and METTL3.
  • Examining the effect of coilin suppression on METTL3 localization, phosphorylation, and complex formation with METTL14 and WTAP.

Main Results:

  • Coilin suppression led to reduced m6A modification on primary Let7a and miR-21.
  • Suppression of coilin decreased the protein levels of hnRNPA2B1 and METTL3.
  • Coilin interacts with METTL3, and its suppression affects METTL3's nucleoplasmic localization and phosphorylation.
  • Coilin depletion disrupted the METTL3 complex, including METTL14 and WTAP.

Conclusions:

  • Coilin is involved in mediating m6A RNA methylation.
  • Coilin participates in miRNA biogenesis through its influence on m6A modification and the METTL3 complex.
Keywords:
Cajal bodyCoilinMETTL3MethylationMicroRNA

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