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A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues
Published on: December 5, 2016
m6A regulator-mediated RNA methylation modification patterns and immune microenvironment infiltration
Deyang Sun1, Huan Yang1, Liming Fan1
1The First Clinical College, Zhejiang Chinese Medical University, Hangzhou, China.
Abstract:
N6-methyladenosine (m6A) modification is one of the most prevalent RNA modification forms of eukaryotic mRNA and is an important post-transcriptional mechanism for regulating genes. However, the role of m6A modification in the regulation of severe asthma has never been reported. Thus, we aimed to investigate the m6A regulator-mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in severe asthma. In this study, 87 healthy controls and 344 severe asthma cases from the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) programme were used to systematically evaluate the m6A modification patterns mediated by 27 m6A regulators and to investigate the effects of m6A modification on immune microenvironment characteristics. We found that 16 m6A regulators were abnormal and identified two key m6A regulators (YTHDF3 and YTHDC1) and three m6A modification patterns. The study of infiltration characteristics of immune microenvironment found that pattern 2 had more infiltrating immune cells and more active immune response. Besides, it was found that the eosinophils which are very important for severe asthma were affected by YTHDF3 and EIF3B. We also verified key m6A regulators with merip-seq and found that they were mainly distributed in exons and enriched in 3'UTR. In conclusion, our findings suggested that m6A modification plays a key role in severe asthma, and may be able to guide the future strategy of immunotherapy.
Insights
N6-methyladenosine (m6A) RNA modification patterns are altered in severe asthma, impacting immune cell infiltration. Key regulators like YTHDF3 and YTHDC1 offer potential targets for future immunotherapy strategies.
Area of Science:
- Molecular Biology
- Immunology
- Genetics
Background:
- N6-methyladenosine (m6A) is a prevalent mRNA modification regulating gene expression.
- The role of m6A modification in severe asthma pathogenesis remains unexplored.
Purpose of the Study:
- To investigate m6A regulator-mediated RNA methylation patterns in severe asthma.
- To characterize immune microenvironment infiltration in relation to m6A patterns.
Main Methods:
- Analysis of 27 m6A regulators in 87 healthy controls and 344 severe asthma cases (U-BIOPRED cohort).
- Systematic evaluation of m6A patterns and immune cell infiltration.
- Validation of key regulators using merip-seq.
Main Results:
- 16 m6A regulators showed abnormal expression in severe asthma.
- Two key regulators (YTHDF3, YTHDC1) and three distinct m6A patterns were identified.
- Pattern 2 was associated with increased immune cell infiltration and activity, and eosinophil levels were linked to YTHDF3 and EIF3B.
Conclusions:
- m6A modification plays a significant role in severe asthma.
- Identified m6A regulators and patterns may guide future immunotherapy strategies for severe asthma.
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