Bioinformatics analysis prioritizes 2,505 Arabidopsis genes linking m6A and alternative polyadenylation

The study describes these candidates, collectively called m6APAreg genes, as priorities for future functional testing rather than experimentally established members of a shared pathway. Published in BMC Plant Biology , the research combines modification profiles, measurements of polyadenylation-site use and protein-interaction networks to infer possible connections between the two post-transcriptional processes. The researchers assembled 56 methylated RNA immunoprecipitation sequencing, or MeRIP-seq, datasets generated under diverse genetic backgrounds and stress conditions.

Within these datasets, they performed multi-sample correlation analyses to compare m6A modification levels with APA usage, including the relative use of distal poly(A) sites. They then used a random walk with restart algorithm to screen protein–protein interaction networks for genes associated with the inferred m6A–APA relationship. This integrated framework produced the set of 2,505 m6APAreg candidates and was designed to prioritize genes for subsequent experimental investigation rather than to prove that each gene directly controls both processes.

Functional enrichment analysis showed that the candidate genes were significantly enriched in pathways related to metabolism, stress response and developmental regulation. This result indicates that the genes annotated to these categories are represented disproportionately in the candidate set; it does not by itself establish that every candidate participates in those biological processes. The researchers also constructed multilayered regulatory networks integrating m6APAreg genes with microRNAs, transcription factors and poly(A) factors.

These networks were used to examine a possible regulatory hierarchy involving RNA modification, transcriptional control and RNA 3′-end processing. Published datasets provided orthogonal support for the computational prioritization. The analysis found a higher binding rate for the m6A reader CPSF30-L among m6APAreg genes, together with stronger poly(A) signals.

The association is consistent with a possible connection between m6A-related regulation and polyadenylation, but the reported evidence does not demonstrate that CPSF30-L directly regulates all or any specific candidate gene. Sample-specific analyses further characterized condition-dependent patterns: the inferred direction of regulatory relationships and the functional modules associated with the m6A–APA axis could change in response to genetic background and environmental stress. Because these patterns were derived through computational analysis of associated datasets, they indicate context-dependent associations rather than demonstrated causal effects.

The authors characterize the work as the first systematic attempt to prioritize candidate genes associated with an m6A–APA regulatory module in Arabidopsis. Its main contribution is a framework and a reservoir of 2,505 candidates for future studies of plant development and stress responses, with possible relevance to crop improvement. The principal limitation is that the prioritized relationships require direct functional validation through experiments that are outside the reported computational framework.

The findings therefore offer a system-wide map of inferred coordination between an m6A RNA modification and alternative polyadenylation, providing testable leads for future research on how plants may regulate gene expression through changes in RNA processing.

Subject of Research: Computational identification of candidate genes linking m6A modification and alternative polyadenylation in Arabidopsis thaliana

Article Title: System-wide identification and regulatory network analysis of m⁶A-APA associated genes in Arabidopsis Thaliana

Article References: Qian, F., Liang, J., Ye, M., Liu, Z., & Wu, X. (2026). System-wide identification and regulatory network analysis of m⁶A-APA associated genes in Arabidopsis Thaliana. BMC Plant Biology. https://doi.org/10.1186/s12870-026-09604-5

Image Credits: AI Generated

DOI: 10.1186/s12870-026-09604-5

Keywords: Arabidopsis thaliana, m6A modification, alternative polyadenylation, MeRIP-seq, gene regulation, epitranscriptomics, protein interactions, regulatory networks, plant stress responses, bioinformatics, System-wide, identification