The Monticelli Lab published a study in Nature Communications revealing the role of mRNA methylation in restraining mast cell functions.
Bellinzona, July 19, 2023 – Mast cells are cells of the innate immune system with crucial roles in allergy and asthma. Aberrant mast cell responses can lead to highly reduced quality of life and even life-threating conditions, as in the case of anaphylactic reactions. Many mechanisms contribute to the regulation of mast cell functions and responses. In this study, published in Nature Communications and performed jointly by Cristina Leoni and Marian Bataclan from the IRB (affiliated to USI), the Monticelli lab found that the adenosine methylation (m6A) of messenger RNAs (mRNAs) encoding inflammatory cytokines is important to restrain mast cell responses. Deletion of different components of the methyltransferase complex, important for mRNA methylation, enhanced the stability of transcripts encoding inflammatory molecules, leading to exacerbated inflammation.
This study is relevant because it establishes the importance of mRNA methylation in modulating mast cell functions. Moreover, this study introduces a new methodology to modify mast cells in vitro using the CRISPR-Cas9 gene-editing approach. The future challenge will be to identify how exactly this regulation is achieved in mast cells.
This work was performed in collaboration with the lab of Vigo Heissmeyer (LMU Munich – Germany).
Deletion of Mettl3, the enzymatic component of the m6A methyltransferase complex, enhanced the stability (red line) of the transcripts encoding the inflammatory cytokines IL-13 and TNF.