HC-Pro inhibits HEN1 methyltransferase activity, leading to autophagic degradation of AGO1

Zhao-Jun Pan, Wei-Lun Wei, Phuong-Anh Tran, Ru-Ying Fang, Thanh Ha Pham, John L. Bowman, Chao-Tzu Chung, Bing-Nan Shen, Ju-Ting Yang, Han-Han Chang, Wann-Neng Jane, Chiung-Hsiang Cheng, Chia-Chi Wang, Hsin-Yi Wu, Syuan-Fei Hong, Qian-Wen Shang, Sin-Fen Hu, Pin-Chun Lin, Fu-Hui Wu, Choun-Sea Lin, Yu-Ling Hung, Tang-Long Shen and Shih-Shun Lin ()
Additional contact information
Zhao-Jun Pan: National Taiwan University
Wei-Lun Wei: National Taiwan University
Phuong-Anh Tran: National Taiwan University
Ru-Ying Fang: National Taiwan University
Thanh Ha Pham: National Taiwan University
John L. Bowman: Monash University
Chao-Tzu Chung: National Taiwan University
Bing-Nan Shen: National Taiwan University
Ju-Ting Yang: National Taiwan University
Han-Han Chang: National Taiwan University
Wann-Neng Jane: Academia Sinica
Chiung-Hsiang Cheng: National Taiwan University
Chia-Chi Wang: National Taiwan University
Hsin-Yi Wu: National Taiwan University
Syuan-Fei Hong: National Taiwan University
Qian-Wen Shang: National Taiwan University
Sin-Fen Hu: National Taiwan University
Pin-Chun Lin: National Taiwan University
Fu-Hui Wu: Academia Sinica
Choun-Sea Lin: Academia Sinica
Yu-Ling Hung: National Taiwan University
Tang-Long Shen: National Taiwan University
Shih-Shun Lin: National Taiwan University

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Helper-component proteinase (HC-Pro), encoded by potyviruses, function as viral suppressors of RNA silencing (VSRs). Despite their conserved role, HC-Pros share approximately 40% similarity, implying potential differences in VSR efficiency, particularly in their ability to inhibit HEN1 methyltransferase activity. This study investigated the inhibitory potential of HC-Pros from different potyviruses in transgenic plants. P1/HC-Pro from turnip mosaic virus (P1/HC-ProTu) exhibited the most potent inhibition of HEN1, followed by P1/HC-Pro from zucchini yellow mosaic virus (P1/HC-ProZy), while P1/HC-Pro from tobacco etch virus (P1/HC-ProTe) showed the weakest inhibitory effect. These differential effectual effects corresponded to variations in unmethylated microRNAs (unMet-miRNAs) accumulation across the transgenic lines. Fluorescence resonance energy transfer (FRET) analysis indicated that HC-ProTu recruits HEN1 and ATG8a to HC-Pro bodies (H-bodies) and indirectly associates with AGO1, potentially influencing the assembly of the RNA-induced silencing complex (RISC) and leading to the accumulation of free-form miRNA duplexes. The ability of HC-ProTu to sequester HEN1 and AGO1 in H-bodies may, therefore, modulate miRNA loading. This observation aligns with the finding that P1/HC-ProTu plants harbored approximately 50% unMet-miRNAs and exhibited the lowest AGO1 levels, suggesting a positive correlation between HEN1 inhibition and autophagic degradation of AGO1. Interestingly, unMet-miRNAs are absent in the AGO1 of P1/HC-ProTu plants but reappeared in P1/HC-ProTu/hen1-8/heso1-1 plants, accompanied by signs of AGO1 recovery. These findings highlight the functional diversity of HC-Pro VSRs and provide new insights into their differential effects on miRNA methylation, RISC assembly, and the regulation of RNA silencing pathways.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-56320-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56320-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-56320-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().