eIF4A, a target of siRNA derived from rice stripe virus, negatively regulates antiviral autophagy by interacting with ATG5 in Nicotiana benthamiana.

eIF4A, a target of siRNA derived from rice stripe virus, negatively regulates antiviral autophagy by interacting with ATG5 in Nicotiana benthamiana.
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eIF4A 是源自水稻条纹病毒的 siRNA 靶标,通过与本塞姆氏烟草中的 ATG5 相互作用来负向调节抗病毒自噬

DOI:
10.1371/journal.ppat.1009963
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发表时间:
2021-09
期刊:
影响因子:
6.7
通讯作者:
Yan F
Yan F
中科院分区:
医学1区
文献类型:
--
作者:
Zhang X;Yin Y;Su Y;Jia Z;Jiang L;Lu Y;Zheng H;Peng J;Rao S;Wu G;Chen J;Yan F

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自噬是由病毒感染诱导的,在植物中具有抗病毒功能,但其潜在机制尚不清楚。我们先前通过靶向宿主真核细胞翻译起始因子4A(EIF4A)mRNA的沉默,鉴定了一种源于水稻条纹病毒(RSV)RNA4的病毒小干扰RNA(VsiRNA),它导致了该病毒引起的叶片扭曲和发育迟缓症状。此外,自噬通过降解RSV p3蛋白发挥抗病毒作用,RSV p3蛋白是RNA沉默的抑制因子。在这里,我们证明了eIF4A在本氏烟草中作为自噬的负调控因子。沉默NbeIF4A激活了自噬,并通过促进p3的自噬降解来抑制RSV感染。进一步分析表明,NbeIF4A与NbATG5相互作用,并干扰其与ATG12的相互作用。过表达NbeIF4A可抑制NbATG5激活的自噬。此外,靶向NbeIF4A mRNA进行切割的vsiRNA-4A的表达通过沉默NbeIF4A而诱导自噬。最后,我们证明了RSV的自然宿主水稻中的eIF4A也与OsATG5相互作用并抑制OsATG5激活的自噬,指出eIF4A作为抗病毒自噬的负调控因子具有保守的功能。综上所述,这些结果表明eIF4A通过与ATG5相互作用负向调节抗病毒自噬,其mRNA被病毒来源的siRNA识别,导致其沉默,从而诱导抗病毒感染的自噬。自噬是由病毒感染诱导的,在植物中具有抗病毒功能,但其潜在机制尚不清楚。在这里,我们证明了eIF4A是自噬的负调节因子,它通过抑制ATG5的功能而起作用,ATG5是自噬的关键成分。我们以前报道过NbeIF4A转录本被水稻条纹病毒(RSV)来源的siRNA切割,自噬通过降解RSV p3蛋白发挥抗病毒作用,RSV p3蛋白是RNA沉默的抑制因子。综上所述,我们的发现揭示了一种新的机制,即抗病毒自噬的负调控因子识别病毒来源的siRNA并牺牲自己来诱导自噬,从而抑制病毒感染。
Autophagy is induced by viral infection and has antiviral functions in plants, but the underlying mechanism is poorly understood. We previously identified a viral small interfering RNA (vsiRNA) derived from rice stripe virus (RSV) RNA4 that contributes to the leaf-twisting and stunting symptoms caused by this virus by targeting the host eukaryotic translation initiation factor 4A (eIF4A) mRNA for silencing. In addition, autophagy plays antiviral roles by degrading RSV p3 protein, a suppressor of RNA silencing. Here, we demonstrate that eIF4A acts as a negative regulator of autophagy in Nicotiana benthamiana. Silencing of NbeIF4A activated autophagy and inhibited RSV infection by facilitating autophagic degradation of p3. Further analysis showed that NbeIF4A interacts with NbATG5 and interferes with its interaction with ATG12. Overexpression of NbeIF4A suppressed NbATG5-activated autophagy. Moreover, expression of vsiRNA-4A, which targets NbeIF4A mRNA for cleavage, induced autophagy by silencing NbeIF4A. Finally, we demonstrate that eIF4A from rice, the natural host of RSV, also interacts with OsATG5 and suppresses OsATG5-activated autophagy, pointing to the conserved function of eIF4A as a negative regulator of antiviral autophagy. Taken together, these results reveal that eIF4A negatively regulates antiviral autophagy by interacting with ATG5 and that its mRNA is recognized by a virus-derived siRNA, resulting in its silencing, which induces autophagy against viral infection. Autophagy is induced by viral infection and has antiviral functions in plants, but the underlying mechanism is poorly understood. Here we demonstrate that eIF4A is a negative regulator of autophagy in N. benthamiana and rice that acts by inhibiting the function of ATG5, a key component of autophagy. We previously reported that NbeIF4A transcripts are targeted for cleavage by rice stripe virus (RSV)-derived siRNA and that autophagy plays an antiviral role by degrading RSV p3 protein, a suppressor of RNA silencing. Together, our findings reveal a novel mechanism in which a negative regulator of antiviral autophagy recognizes a virus-derived siRNA and sacrifices itself to induce autophagy, which inhibits viral infection.
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