Cationic amyloidogenic peptides in mammalian seminal fluid undergo liquid-liquid phase separation with RNA to form functional amyloid fibrils that are internalized by sperm through receptor-mediated endocytosis and deliver translationally active RNA cargo to embryos during fertilization, establishing a novel amyloid-based mechanism for extracellular RNA trafficking to the germline.

Seminal fluid RNA is essential for embryonic development, but the mechanism by which extracellular RNA is transferred from seminal fluid to sperm remains unclear. Here, we identify a role for functional amyloid fibrils in seminal fluid that bind and traffic RNA to mammalian sperm and, upon fertilization, the zygote. We show that highly cationic peptides in seminal fluid phase separate with RNA to form amyloid fibrils. Cryo-electron tomography reveals that these amyloid fibrils are internalized by sperm. Furthermore, biophysical and in vitro fertilization experiments show that amyloid-bound RNA reaches the zygote where molecular chaperones control release of RNA for translation. Our work uncovers a mechanism for RNA trafficking from seminal fluid to the zygote, establishing amyloid fibrils as potential tools for RNA delivery during fertilization.