tRNA-derived RNA processing in sperm transmits non-genetically inherited phenotypes to offspring in C. elegans
The environment encountered by an organism can modulate epigenetic information in the gametes to transmit non-genetically inherited phenotypes to offspring. In mouse models, the diet of males regulates specific tRNA-derived RNAs (tDRs) in sperm. After fertilization, tDRs regulate embryonic gene expression and generate metabolic phenotypes in adult offspring through uncharacterized changes during development. Here we demonstrate that in C. elegans tDRs also accumulate in sperm and can similarly transmit epigenetically inherited phenotypes to offspring. We identify the RNaseT2 enzyme, rnst-2, as a regulator of C. elegans' tDR accumulation. RNST-2 processes or degrades tRNA-halves, leading to the accumulation of shorter <30 nt fragments. This rnst-2 dependent regulation of tDR length distribution modulates specific tDRs in sperm which, after fertilization, regulate early embryonic and developmental gene expression, leading to adaptive phenotypes in progeny. Our findings establish tDRs as a deeply conserved carrier of intergenerational epigenetic information and position the worm as a model for dissecting paternal non-genetic inheritance mechanistically. Overall design: Small RNA-seq on adult C. elegans males and females, as well as sperm. mRNA-seq on adult C. elegans males and females. Single embryo RNA-seq on C.elegans 2- and 8-cell embryos.