A lineage-specific selective autophagy receptor module mediates P-body turnover

Area of Science:

• Cell Biology
• Molecular Biology
• Plant Science

Background:

• Processing bodies (P-bodies) are crucial for RNA metabolism in eukaryotes.
• Mechanisms of P-body assembly are known, but their selective turnover pathways are not well understood.

Purpose of the Study:

• To identify the molecular mechanisms governing P-body selective turnover.
• To investigate the role of conserved decapping proteins in this process.
• To explore the evolutionary conservation and potential applications of this pathway.

Main Methods:

• Utilized the model plant Marchantia polymorpha for studying P-body turnover.
• Investigated the interaction between decapping proteins (EDC4, DCP1) and autophagy receptor ATG8.
• Employed genetic mutations to disrupt ATG8-interacting motifs and assessed P-body degradation.
• Performed heterologous expression of plant proteins in human cells.

Main Results:

• Identified EDC4 and DCP1 as a selective autophagy receptor pair for P-body turnover in Marchantia polymorpha.
• MpEDC4 binds ATG8 via a canonical motif, while MpDCP1 uses a novel reverse motif.
• Disrupting these motifs impairs autophagic degradation of P-bodies, indicating a cooperative mechanism.
• This ATG8-binding function is lineage-specific, absent in Arabidopsis and human orthologs.
• Heterologous expression of MpEDC4 in human cells enhanced degradation of α-synuclein.

Conclusions:

• Uncovered an evolutionary link between RNA metabolism and selective autophagy through a novel cooperative receptor mechanism.
• The identified plant-specific autophagic pathway for P-body turnover has potential for cross-kingdom engineering of targeted protein degradation.
• Findings open new avenues for therapeutic strategies targeting proteinopathies like Parkinson's disease.