HC-Pro inhibits HEN1 methyltransferase activity, leading to autophagic degradation of AGO1
Journal
Nature Communications
Journal Volume
16
Journal Issue
1
ISSN
2041-1723
Date Issued
2025-03-13
Author(s)
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
Hsin-Yi Wu
Syuan-Fei Hong
Qian-Wen Shang
Sin-Fen Hu
Pin-Chun Lin
Fu-Hui Wu
Choun-Sea Lin
Yu-Ling Hung
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.
Publisher
Springer Science and Business Media LLC
Description
Article number: 2503
Type
journal article