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.
Authors
- Tingxuan Xu
- Xinjie Li (ORCID: https://orcid.org/0000-0002-1825-9673)
- Jiaying Liu (ORCID: https://orcid.org/0000-0001-8108-8064)
- Sheng Liu (ORCID: https://orcid.org/0000-0001-5119-0324)
- Xin Li (ORCID: https://orcid.org/0000-0001-8328-4894)
- Weihao Pan
- Xuan Jiang
Institutions
- National Sun Yat-sen University (TW)
- Sun Yat-sen University (CN)
- The Seventh Affiliated Hospital of Sun Yat-sen University (CN)
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
- Field-Weighted Citation Impact
- 0.00