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| Item Type: | Article |
|---|---|
| Title: | Comprehensive m(6)A landscape from direct RNA sequencing reveals SYNPO2L RNA isoform regulation mechanisms in heart failure |
| Creators: |
Xu, Zhihan  ORCID: https://orcid.org/0009-0009-4574-930X, Tian, Chi ORCID: https://orcid.org/0000-0002-6093-5858, Chan, Jun Wei, Tew, Wikie, Tang, Galvin L.Q., Qi, Rujie, Tao, Zheyi, Yim, Daniel G.R. ORCID: https://orcid.org/0000-0001-6153-4725, Cui, Liang, Luu, Danh Anh Tuan, Amrute, Junedh M. ORCID: https://orcid.org/0000-0002-6851-0168, Tergaonkar, Vinay, Lee, Chang Jie Mick and Foo, Roger S.Y. ORCID: https://orcid.org/0000-0002-8079-4618
|
| Abstract: | Accumulating evidence suggests that epitranscriptomic regulation, particularly the m(6)A modification, contributes to heart failure progression. However, modification dynamics are not yet mapped and studied at base resolution and transcript isoform level. Here we use Nanopore direct RNA sequencing to profile m(6)A remodeling at transcriptome-wide and site-specific resolution in a mouse heart failure model. We identify thousands of differentially methylated sites with distinct sequence motifs and associations with RNA regulatory and cardiac function processes. Cross-species comparison reveals conserved m(6)A regulatory features in mouse and human heart failure. Isoform-resolved analysis further uncovers co/posttranscriptional regulation events involving isoform switching and m(6)A regulation in the SYNPO2L transcript. Mechanistically, m(6)A modification, alternative promoter usage and associated regulatory elements collectively explain this observation. Overall, our study provides a comprehensive, high-resolution characterization of m(6)A landscape and its remodeling in heart failure. Isoform-level regulation exemplifies an underappreciated shaping of RNA expression and modification. |
| Keywords: | Animal Disease Models, Epitranscriptome, Epitranscriptomics, Heart Failure, Inbred C57BL Mice, Nanopore Sequencing, RNA Isoforms, RNA Methylation, RNA Sequence Analysis, Animals, Mice |
| Source: | Nature Cardiovascular Research |
| ISSN: | 2731-0590 |
| Publisher: | Springer Nature |
| Volume: | 5 |
| Number: | 11 |
| Page Range: | 1213-1230 |
| Date: | November 2026 |
| Official Publication: | https://doi.org/10.1038/s44161-026-00898-0 |
| PubMed: | View item in PubMed |
| Related to: |
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