N 6-methyladenosine modifications stabilize phosphate starvation response–related mRNAs in plant adaptation to nutrient-deficient stress

Kai Liu, Xiaojia Wang, Jingyi Wang, Shuman Wang, Haiyan Bai, Weiguo Dong, Lulu Qiao, Qiongli Jin, Zhonghui Zhang, Guan-Zheng Luo and Zhiye Wang ()
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Kai Liu: Zhejiang University
Xiaojia Wang: Zhejiang University
Jingyi Wang: Zhejiang University
Shuman Wang: Zhejiang University
Haiyan Bai: South China Normal University
Weiguo Dong: Zhejiang University
Lulu Qiao: Zhejiang University
Qiongli Jin: Zhejiang University
Zhonghui Zhang: South China Normal University
Guan-Zheng Luo: Sun Yat-sen University
Zhiye Wang: Zhejiang University

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract N6-methyladenosine (m6A), an abundant internal mRNA modification, is induced by various stress conditions and post-transcriptionally regulates gene expression. However, how m6A modifications help plants respond to nutrient-deficiency stress remains unclear. Here, we profile high-confidence m6A modifications in Arabidopsis transcriptome-wide under normal and inorganic orthophosphate (Pi)–deficient conditions (−P). High-confidence m6A modifications are identified using synthetic modification-free RNA libraries for systematic calibration. Pi starvation induces widespread m6A modifications, mediated by the Pi starvation response (PSR) master regulator PHOSPHATE STARVATION RESPONSE1 (PHR1) and its family members. Many Pi starvation–induced (PSI) m6A modifications occur on PSR-related mRNAs, including PHR1. In addition, PHR1 proteins interact with the m6A writers MRNA ADENOSINE METHYLASE (MTA) and METHYLTRANSFERASE B (MTB) in nuclei under −P conditions. m6A modifications facilitate systemic PSR signaling, as reflected by the reduced Pi content and PSR signaling in a knockdown artificial miRNA line targeting MTA, which shows a global decrease in m6A. Transcriptome-wide mRNA decay analysis reveals that PSI-m6A increases the stability of PSR-related mRNAs, but not through alternative polyadenylation site shifts. Analysis of transgenic plants with mutations in m6A loci demonstrates that m6A stabilizes PHR1 transcripts via a positive feedback loop. Our findings indicate that PSI-m6A modifications facilitate PSR signaling by enhancing the stability of certain mRNAs, shedding light on the role of m6A modifications in nutrient stress responses in plants.

Date: 2025
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DOI: 10.1038/s41467-025-59331-y

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