Human sperm heads harbour modified YsRNA as transgenerationally inherited non-coding RNAs

The presence of regulatory important RNAs in oocytes is undisputed, whereas the RNA payload in spermatozoa and its biogenesis, modifications and regulatory influence in the zygote and early embryogenesis is enigmatic. For humans, we herein describe small YRNA fragments (YsRNA) in sperm heads, the correlate of the zygotic male pronucleus, as paternal contribution to the zygote. We trace the biogenesis of these YsRNAs from source YRNAs with respect to their 5 and 3 modifications. Both the length and modifications make these YsRNAs reminiscent of canonical piRNAs albeit not encoded in piRNA clusters. We track YsRNAs exclusively in mature sperm heads to the exclusion of earlier stages of spermatogenesis. This suggests an important role of the epididymis as a hub for a vesicle-mediated transfer and modification of epigenetic information related to YsRNA between soma and germline in humans. Full length YRNA (100nt) binds to the RNA chaperone Ro60, and functions as a gatekeeper, for misfolded RNA. We determined Ro60 bound lincRNA profiles and checked, if full length YRNA is associated with Ro60. From that we hypothesize, that a molar excess of YsRNA might prevent YRNAs from correct folding and Ro60-association thus enhancing RNA chaperoning in the zygote and early embryo.