大鼠附睾精子穿孔体含具生殖颗粒特征的淀粉样蛋白/RNA凝聚体,并表现朊病毒样传播活性
Amyloid/RNA Condensates with Germ Granule Characteristics Are Present in Rat Epididymal Spermatozoa and Exhibit Prion-Like Propagation Activity
摘要
该预印本以大鼠附睾精子为对象,报道其头部穿孔体(perforatorium,源自细胞质的结构,参与受精后早期事件)中存在生殖颗粒样凝聚体。这些凝聚体含有进化上保守的生殖颗粒标志物和小非编码 RNA,并富集淀粉样蛋白,包括临床相关的淀粉样蛋白 AR 与 TDP43。穿孔体提取物可在体外作为“分子种子”,模板化重组 AR 与 TDP43 的淀粉样组装,表现朊病毒样传播行为。作者据此提出,精子生殖颗粒样结构可能是环境编码信息经非孟德尔、蛋白基机制传递给胚胎的载体;但原文尚未见组学与功能验证细节。
原文摘要
ABSTRACT Environmental exposures to the germline can alter its epigenome resulting in new traits being acquired by offspring. While the epigenetic carrier in mammalian spermatozoa remains unknown, studies in C.elegans show that amyloids and sperm-specific populations of germ granules— phase-separated biomolecular condensates enriched in RNA-binding proteins and small noncoding RNAs— transmit heritable epigenetic phenotypes to descendant cells. Here we discovered that rat epididymal spermatozoa contain germ granule-like condensates in the head perforatorium, a cytoplasmic derived structure that participates in early post-fertilization events. The perforatoria condensates contain evolutionarily conserved germ granule markers and small noncoding RNAs and are enriched in amyloid, including those of the clinically relevant amyloidogenic proteins androgen receptor (AR) and TDP43. Further, perforatoria extracts exhibit prion-like propagation behavior by functioning as molecular seeds to template amyloid assembly in recombinant AR and TDP43. We propose that nature has conserved sperm germ granule-like structures throughout evolution to allow an organism to respond and adapt to a changed environment by passing environmentally encoded information to the embryo via a non-Mendelian protein-based mechanism of inheritance.
推荐理由:把精子表观遗传载体从 DNA 甲基化/非编码 RNA 扩展到相分离的淀粉样蛋白凝聚体,并提出可体外“播种”的朊病毒样机制,概念新颖、与男性生殖核心问题直接相关;但为预印本,样本量、定量与体内功能验证尚未可见,需谨慎解读。
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