Sperm-derived RNAs improve the efficiency of somatic cell nuclear transfer (SCNT) through promoting R-loop formation.

Abstract

Mammalian sperm and oocytes are haploid cells that carry parental genetic and epigenetic information for their progeny. The cytoplasm of oocytes is also capable of reprograming somatic cells to establish totipotency through somatic cell nuclear transfer (SCNT). However, epigenetic barriers seriously counteract SCNT reprogramming. Here, we found that sperm-derived RNAs elevated chromatin accessibility of nuclear donor cells concurrent with the appearance of increased RNA amount and decreased cell proliferation, instead of activating DNA damage response. Additionally, tri-methylation of lysine 9 on histone H3 (H3K9me3) and the H3K9 methyltransferase SUV39H2 were significantly downregulated by the sperm-derived RNA treatment. Our findings thus raise a fascinating possibility that sperm RNA-induced R-loops may activate gene expression and chromatin structure, thereby promoting SCNT reprogramming.