Degradation of the antiviral component ARGONAUTE1 by the autophagy pathway

Abstract

Posttranscriptional gene silencing (PTGS) mediated by siRNAs is an evolutionarily conserved antiviral defense mechanism in higher plants and invertebrates. In this mechanism, viral-derived siRNAs are incorporated into the RNA-induced silencing complex (RISC) to guide degradation of the corresponding viral RNAs. In Arabidopsis, a key component of RISC is ARGONAUTE1 (AGO1), which not only binds to siRNAs but also carries the RNA slicer activity. At present little is known about posttranslational mechanisms regulating AGO1 turnover. Here we report that the viral suppressor of RNA silencing protein P0 triggers AGO1 degradation by the autophagy pathway. Using a P0-inducible transgenic line, we observed that AGO1 degradation is blocked by inhibition of autophagy. The engineering of a functional AGO1 fluorescent reporter protein further indicated that AGO1 colocalizes with autophagy-related (ATG) protein 8a (ATG8a) positive bodies when degradation is impaired. Moreover, this pathway also degrades AGO1 in a nonviral context, especially when the production of miRNAs is impaired. Our results demonstrate that a selective process such as ubiquitylation can lead to the degradation of a key regulatory protein such as AGO1 by a degradation process generally believed to be unspecific. We anticipate that this mechanism will not only lead to degradation of AGO1 but also of its associated proteins and eventually small RNAs.

A BAR-Domain Protein SH3P2, Which Binds to Phosphatidylinositol 3-Phosphate and ATG8, Regulates Autophagosome Formation in Arabidopsis

“…Since SH3P2 has a membrane-remodeling domain, it is likely that an interaction between SH3P2 and ATG8 promotes membrane deformation for developing autophagosome. Recently, selective autophagy has been identified in plants, and the ATG8 family interacting motif has emerged as the molecular basis for ATG8 to recognize cargo(s) or other proteins in regulating autophagy (Suttangkakul et al, 2011;Svenning et al, 2011;Vanhee et al, 2011;Derrien et al, 2012;Floyd et al, 2012;Honig et al, 2012). Since SH3P2 signals were detected inside the vacuole after autophagy induction (Figures 1Bc and 1Bd), such an SH3P2-ATG8 interaction may target SH3P2 for degradation to regulate the turnover of autophagy.…”

MicroRNA and autophagy—C. elegans joins the crew

“…The recent demonstration, in both human cells and plants, that autophagy is indeed an integral part of miRNA homeostasis [1,2], prompted Zhang and Zhang to explore whether the same was true in C. elegans. They first used a reverse genetic approach based on well-characterized developmental defects shown by animals defective for miRNA biogenesis or action, including the reiteration of stage-specific cell proliferation programmes known as 'heterochronic' defects.…”

“…In fact, this endeavour should be considered a priority if the various tenants of miRNA biology are to be fully understood through modifier gene identification but also interactome studies. A second interesting aspect emerging from the work of Zhang and Zhang, and others [1,2], is the notion that autophagy is part of a global homeostatic regulatory mechanism that prevents overt perturbations to the miRNA pathway. Whilst such perturbations might be artificially induced genetically, as in the present study, they will probably arise naturally through various stresses of abiotic or biotic origin.…”

“…Whilst such perturbations might be artificially induced genetically, as in the present study, they will probably arise naturally through various stresses of abiotic or biotic origin. It is noteworthy that the role of autophagy in the plant miRNA pathway was discovered through the study of the viral virulence factor P0, which suppresses antiviral gene silencing by increasing the turnover of AGO1 through autophagy [2]. Unveiling the mode of action of P0 revealed that selective AGO1 degradation is, in fact, part of a normal regulatory process.…”

“…In addition, astrocytes respond to acute and chronic injury by hypertrophy and induced proliferation. Notably, astrocytes in the mammalian brain represent a highly heterogeneous population and the exact cellular identity of the astrocytic response in the damaged brain remains largely unknown (for a review see [2]). Thus, live-imaging and single-cell studies are required to unravel the complexity of astrocyte behaviour and distinguish between the good and the bad effects of astrocytic activation on brain function and tissue homeostasis in response to acute and chronic injury.…”