Amyloid-mediated RNA uptake by sperm for embryonic delivery

Seminal fluid (SF) RNA is essential for embryonic development, but the mechanism by which extracellular RNA is transferred from SF to sperm remains unclear. Here, we identify a role for functional amyloid fibrils in SF that bind and traffic RNA to mammalian sperm and, upon fertilization, to the zygote. We show that highly cationic peptides in SF phase separate with RNA to form amyloid fibrils. Cryo-electron tomography (cryo-ET), volume electron microscopy (volume EM), and fluorescence live-cell imaging reveal that these amyloid fibrils are internalized by mammalian sperm. Furthermore, biophysical and in vitro fertilization (IVF) experiments show that amyloid-bound RNA reaches the zygote, where molecular chaperones can control RNA dissociation from amyloid fibrils. Our work uncovers a mechanism for RNA trafficking from SF to the zygote, establishing amyloid fibrils as potential tools for RNA delivery during fertilization.