Evidence map›Paper›PMID 40456740›Full record

ArticleNature communications2025

Single-molecule direct RNA sequencing reveals the shaping of epitranscriptome across multiple species.

Ying-Yuan Xie, Zhen-Dong Zhong, Hong-Xuan Chen, Ze-Hui Ren, Yuan-Tao Qiu, Ye-Lin Lan, Fu Wu, Jin-Wen Kong, Ru-Jia Luo, Delong Zhang and 7 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed.

  1. Review
  2. Review
  3. Single-molecule mbioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. mBiomolecules · 2026
    Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. NNature reviews. Cancer · 2026
    Review
  13. Review
  14. Article
  15. Review
  16. Comprehensive discovery of mNature communications · 2025
    Article
  17. Review
  18. Review
  19. Article
  20. FTO depletion does not alter mbioRxiv : the preprint server for biology · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Ying-Yuan Xie *State Key Laboratory of Biocontrol, MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
Zhen-Dong Zhong *State Key Laboratory of Biocontrol, MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
Hong-Xuan Chen *State Key Laboratory of Biocontrol, MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
Ze-Hui RenState Key Laboratory of Biocontrol, MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.ORCID http://orcid.org/0000-0001-9599-6581
Yuan-Tao QiuState Key Laboratory of Biocontrol, MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
Ye-Lin LanState Key Laboratory of Biocontrol, MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
Fu WuState Key Laboratory of Biocontrol, MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
Jin-Wen KongState Key Laboratory of Biocontrol, MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
Ru-Jia LuoState Key Laboratory of Biocontrol, MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
Delong ZhangState Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Agriculture, South China Agricultural University, Guangzhou, 510642, China.
Biao-Di LiuState Key Laboratory of Biocontrol, MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
Yang ShuState Key Laboratory of Biocontrol, MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
Feng YinPingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen, 518118, China.
Jian WuState Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Agriculture, South China Agricultural University, Guangzhou, 510642, China.
Zigang LiPingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen, 518118, China.ORCID http://orcid.org/0000-0002-4649-1592
Zhang ZhangState Key Laboratory of Biocontrol, MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China. zhangzhang@mail.sysu.edu.cn.ORCID http://orcid.org/0000-0003-2525-9599
Guan-Zheng LuoState Key Laboratory of Biocontrol, MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China. luogzh5@mail.sysu.edu.cn.ORCID http://orcid.org/0000-0002-6797-9319

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

N6-methyladenosine (m6A) is an essential RNA modification that regulates gene expression and influences diverse cellular processes. Yet, fully characterizing its transcriptome-wide landscape and biogenesis mechanisms remains challenging. Traditional next-generation sequencing (NGS) methods rely on short-reads aggregation, overlooking the inherent heterogeneity of RNA transcripts. Third-generation sequencing (TGS) platforms offer direct RNA sequencing (DRS) at the resolution of individual RNA molecules, enabling simultaneous detection of RNA modifications and RNA processing events. In this study, we introduce SingleMod, a deep learning model tailored for precise detection of m6A modification on individual RNA molecules from DRS data. SingleMod innovatively employs a multiple instance regression (MIR) framework, leveraging extensive methylation-rate labels provided by the quantitative NGS-based method, and achieves ROC AUC and PR AUC of ~0.95 for single-molecule m6A prediction. Applying SingleMod to human cell lines, we systematically dissect the transcriptome-wide m6A landscape at single-molecule and single-base resolution, characterizing m6A heterogeneity in RNA molecules from the same transcript. Through comparative analyzes across eight diverse species, we quantitatively elucidate three distinct m6A distribution patterns correlated with phylogenetic relationships and suggest divergent regulatory mechanisms. This study provides a framework for understanding the shaping of epitranscriptome in a single-molecule perspective.

Indexed as

Epigenesis, GeneticSequence Analysis, RNATranscriptomeAdenosineAnimalsDeep LearningHigh-Throughput Nucleotide SequencingHumansMethylationRNARNA Processing, Post-TranscriptionalAdenosineN-methyladenosineRNA

Identifiers

PMID40456740
PMCPMC12130510

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.