Targeted mRNP-phagy licenses translational activation during cellular metamorphosis

Post-transcriptional mRNA storage and timed reactivation represent fundamental strategies for cellular adaptation, yet the mechanisms enabling selective mRNP remodeling remain enigmatic. Here we identify the MEX3D-HIP1 (MX-H) mRNP-phagy pathway and its executing organelle MXLV (MEX3D-associated lysosomal vesicle) as an evolutionarily conserved system for lysosome-mediated RBP clearance. Through multi-omics profiling and functional studies, we demonstrate that cytosolic MEX3D operates as a dual-function RNA-binding E3 ligase, selectively ubiquitinating repressive RBP (e.g., SF1) on stored mRNAs. This ubiquitination signal recruits HIP1 to assemble MXLV, a specialized autophagic vesicle that resolves translationally silent mRNP complexes through compartmentalized degradation. Genetic ablation of MX-H components disrupts late spermiogenesis by trapping morphogenetic mRNAs in ribonucleoprotein aggregates, while inhibition of MXLV biogenesis suppresses gastric cancer progression through RBP network stabilization. Crucially, MXLV's physiological restriction to male germ cell development creates a therapeutic window for targeting its oncogenic co-option. Our work establishes MXLV as a metamorphic organelle that licenses cellular transformation through mRNP-phagy, revealing how germline-specific membrane trafficking systems are repurposed in pathological proteome remodeling.