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

Area of Science:

• Epigenetics
• Molecular Biology
• Human Reproduction

Background:

• Epigenetic information is usually reprogrammed during development, but some can be inherited, especially via small non-coding RNAs in metazoans.
• While oocyte RNA content is known, the role of sperm RNA in zygote and early embryonic development is largely unclear.

Purpose of the Study:

• To identify and characterize paternal small YRNA fragments (YsRNAs) as a contribution to the human zygote.
• To investigate the biogenesis, dynamics, and potential adaptive function of YsRNAs in human spermatogenesis and early development.

Main Methods:

• Tracing YsRNA biogenesis from source YRNAs, analyzing 5' and 3' modifications.
• Observing YsRNA profile dynamics during spermatogenesis and epididymal maturation.
• Detecting YsRNAs in mature sperm heads and analyzing Ro60-bound non-coding RNAs in sperm.

Main Results:

• Small YRNA fragments (YsRNAs) are identified as a paternal contribution to the human zygote.
• YsRNAs exhibit distinct profiles and dynamics during male germline development, found exclusively in mature sperm heads.
• The study found no YRNA bound to Ro60 in sperm, suggesting a potential mechanism for YsRNA to prevent YRNA-Ro60 interactions.

Conclusions:

• YsRNAs represent a novel form of paternal epigenetic inheritance in humans, originating from YRNAs.
• The epididymis plays a crucial role in transmitting and modifying YsRNA epigenetic information.
• YsRNAs may have an adaptive role by modulating RNA chaperoning through interactions with Ro60, influencing early development.