m⁶A presence and dosage are associated with IGF2BP2 binding, RNA abundance, and translation in mouse heart and liver

N6-methyladenosine (m⁶A), the most prevalent internal modification in mammalian mRNA, contributes to post-transcriptional gene regulation, yet how m⁶A presence and modification intensity relate to gene expression during development remains incompletely understood. Here, by integrating m⁶A-seq, RNA-seq, IGF2BP2 RIP-seq, and Ribo-seq data across developmental trajectories of murine heart and liver, we identify a genome-wide presence-dosage pattern of m⁶A-associated gene regulation. m⁶A-modified transcripts generally show higher baseline expression than unmodified transcripts, whereas increasing modification intensity within m⁶A-modified transcripts is associated with reduced transcript abundance. This dual pattern is linked to the binding behavior of the m⁶A reader IGF2BP2: IGF2BP2 occupancy is enriched on m⁶A-modified transcripts but decreases with higher methylation intensity. Structural equation modeling further supports layered associations among m⁶A status, IGF2BP2 binding, transcript abundance, and ribosome occupancy. Regional analysis of m⁶A peaks also suggests position-dependent relationships with translation efficiency, with 3' UTR m⁶A associated with higher TE and CDS m⁶A associated with lower TE. Together, our study provides a quantitative multi-omic framework for understanding how m⁶A presence and dosage are associated with gene expression and translation during tissue development, and suggests IGF2BP2 binding as a potential mediator of these relationships.

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Publication Details

Journal
RNA
Published
2026-10-29
DOI
https://doi.org/10.1261/rna.081163.126
Primary Topic
RNA modifications and cancer
Type
article
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article

m⁶A presence and dosage are associated with IGF2BP2 binding, RNA abundance, and translation in mouse heart and liver

Tingxuan Xu, Xinjie Li, Jiaying Liu, Sheng Liu et al.
RNA
RNA modifications and cancer
article

m⁶A presence and dosage are associated with IGF2BP2 binding, RNA abundance, and translation in mouse heart and liver

Tingxuan Xu, Xinjie Li, Jiaying Liu, Sheng Liu, Xin Li, Weihao Pan, Xuan Jiang
article en

Abstract

N6-methyladenosine (m⁶A), the most prevalent internal modification in mammalian mRNA, contributes to post-transcriptional gene regulation, yet how m⁶A presence and modification intensity relate to gene expression during development remains incompletely understood. Here, by integrating m⁶A-seq, RNA-seq, IGF2BP2 RIP-seq, and Ribo-seq data across developmental trajectories of murine heart and liver, we identify a genome-wide presence-dosage pattern of m⁶A-associated gene regulation. m⁶A-modified transcripts generally show higher baseline expression than unmodified transcripts, whereas increasing modification intensity within m⁶A-modified transcripts is associated with reduced transcript abundance. This dual pattern is linked to the binding behavior of the m⁶A reader IGF2BP2: IGF2BP2 occupancy is enriched on m⁶A-modified transcripts but decreases with higher methylation intensity. Structural equation modeling further supports layered associations among m⁶A status, IGF2BP2 binding, transcript abundance, and ribosome occupancy. Regional analysis of m⁶A peaks also suggests position-dependent relationships with translation efficiency, with 3' UTR m⁶A associated with higher TE and CDS m⁶A associated with lower TE. Together, our study provides a quantitative multi-omic framework for understanding how m⁶A presence and dosage are associated with gene expression and translation during tissue development, and suggests IGF2BP2 binding as a potential mediator of these relationships.

RNA
National Sun Yat-sen University (TW), Sun Yat-sen University (CN), The Seventh Affiliated Hospital of Sun Yat-sen University (CN)
Good health and well-being
Openalex Percentile: Top 23%
RNA modifications and cancer
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m⁶A presence and dosage are associated with IGF2BP2 binding, RNA abundance, and translation in mouse heart and liver — Tingxuan Xu, Xinjie Li, et al. · RNA (2026) | TGRS Research Map | TGRS