RRC ID 88170
Author Galambos NS, Crocker OJ, Schneider BK, Allerton KS, Gross KE, Schneider AE, Lynch J, Yukselen O, Kucukural A, Conine CC.
Title tRNA-derived RNA processing in sperm transmits non-genetically inherited phenotypes to offspring in C. elegans.
Journal Res Sq
Abstract The environment encountered by an organism can modulate epigenetic information in 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 short <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.
Published 2025-6-6
DOI 10.21203/rs.3.rs-6770943/v1
PII rs.3.rs-6770943
PMID 40502780
PMC PMC12155203
Resource
C.elegans tmC16 tmls1237