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<p>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 <i>C. elegans</i>, tDRs also accumulate in sperm and similarly transmit epigenetically inherited phenotypes to offspring. We identify the RNaseT2 enzyme, <i>rnst-2</i>, as a regulator of <i>C. elegans</i> tDR accumulation. RNST-2 processes or degrades tRNA-halves, to short &lt;30 nt fragments. This <i>rnst-2</i> 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 conserved carrier of intergenerational epigenetic information and position the worm as a model for dissecting paternal non-genetic inheritance mechanistically.</p>

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tRNA-derived RNA processing in sperm transmits non-genetically inherited phenotypes to offspring in C. elegans

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月15日

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  • Nicholas S. Galambos,
  • Olivia J. Crocker,
  • Blair K. Schneider,
  • Kennelly S. Allerton,
  • Katrin E. Gross,
  • Alexandra E. Schneider,
  • Jared Lynch,
  • Onur Yukselen,
  • Alper Kucukural,
  • Colin C. Conine

摘要

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 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, 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 conserved carrier of intergenerational epigenetic information and position the worm as a model for dissecting paternal non-genetic inheritance mechanistically.