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2026年10期
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A germline-specific vesicular structure licenses mRNA activation during spermiogenesis and is hijacked in gastric cancer
A germline-specific vesicular structure licenses mRNA activation during spermiogenesis and is hijacked in gastric cancer
摘要
Post-transcriptional regulation is pivotal for cellular differentiation,yet how translationally silent mRNAs are selectively reactivated remains elusive.Here,we identify the MEX3D-HIP1(MX-H)pathway and its associated organelle,the MEX3D-associated lysosomal vesicle(MXLV),as a shared system governing mRNA activation during spermiogenesis.Our data support a model in which MEX3D acts as an RNA-associated E3 ligase that selectively promotes ubiquitination of RBPs within RBP-mRNA complexes.This ubiquitination signal recruits HIP1,triggering the formation of MXLV,an autophagic vesicle that degrades translationally silent mRNP complexes.Genetic ablation of MX-H components in male germ cells disrupts spermiogenesis,leading to the accumulation of mRNP aggregates and male infertility.Intriguingly,we discovered that this germline-restricted pathway is aberrantly activated in gastric cancer cells,where MXLV biogenesis promotes tumor progression.The strict restriction of MXLV to male germ cells under physiological conditions may provide a unique therapeutic window,suggesting that targeting this pathway could suppress tumor progression while minimizing adverse effects on normal physiolog-ical functions.Our work establishes MXLV as a specialized vesicular structure essential for cellular remodeling during development and reveals how a germline-specific membrane trafficking system is co-opted in pathological proteome remodeling in gastric cancer.
年，卷(期)：
2026, 71(10)
机标分类号：
G2
O
TD402
在线出版日期：
2026年7月23日
