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Spatially resolved m6A profiling using m6A-ARTR-DBiT
Yu Xiao1,2,3, Zhiliang Bai4, Zhuoning Zou1,2
1Department of Chemistry, The University of Chicago, Chicago, IL, USA.
Nature Methods
|June 9, 2026
Summary
We developed m6A-ARTR-DBiT, a new method to map RNA modifications in tissues. This technique reveals how N6-methyladenosine (m6A) distribution relates to gene expression and tissue structure.
Area of Science:
- Molecular Biology
- Epigenetics
- Genomics
Background:
- N6-methyladenosine (m6A) is a crucial RNA modification with diverse regulatory roles.
- The spatial distribution of m6A within tissues is largely unknown, limiting our understanding of its function.
- Existing methods lack the resolution to map m6A distribution while preserving tissue context.
Purpose of the Study:
- To introduce and validate m6A-ARTR-DBiT, a novel assay for spatial m6A profiling.
- To generate high-resolution m6A landscapes in intact mouse tissues.
- To explore the relationship between spatial m6A patterns and gene expression.
Main Methods:
- m6A-ARTR-DBiT assay utilizes reverse-transcription-based detection and deterministic barcoding in tissue.
- Application to mouse embryonic tissues and adult brains, including the hippocampus.
- Pairwise comparison of spatial m6A profiles with spatial transcriptomes.
Main Results:
- Spatially resolved m6A landscapes were generated for mouse embryonic and adult brain tissues.
- Region-associated m6A features were identified across different functional domains.
- Positive correlations were found between m6A levels and the expression of m6A-related enzymes and proteins.
- High-resolution mapping of m6A organization within fine-scale hippocampal structures was achieved.
Conclusions:
- m6A-ARTR-DBiT is a powerful platform for interrogating RNA modification distribution in intact tissues.
- The study provides insights into the link between spatially patterned m6A deposition and gene regulation.
- This method enables systematic identification of tissue-region-specific epitranscriptomic regulation.
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