期刊
SCIENCE ADVANCES
卷 8, 期 47, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abj2029
关键词
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资金
- Cardio-Pulmonary Institute [EXC 2026, 390649896]
- Bayer Foundation
- Max Planck Society
- European Research Council (ERC) under the European Union [AdG 694455-ZMOD, AdG 101021349-TAaGC]
- Leducq Foundation
This study identifies a novel mode of transgenerational epigenetic inheritance called transcriptional adaptation (TA). It demonstrates that mutant mRNA degradation can affect gene expression and modulate the transcriptome of offspring. This finding provides a new perspective on understanding genetic variation and epigenetic inheritance.
Transgenerational epigenetic inheritance (TEI) is mostly discussed in the context of physiological or environmental factors. Here, we show intergenerational and transgenerational inheritance of transcriptional adaptation (TA), a process whereby mutant messenger RNA (mRNA) degradation affects gene expression, in nematodes and zebrafish. Wild-type offspring of animals heterozygous for mRNA-destabilizing alleles display increased expression of adapting genes. Notably, offspring of animals heterozygous for nontranscribing alleles do not display this response. Germline-specific mutations are sufficient to induce TA in wild-type offspring, indicating that, at least for some genes, mutations in somatic tissues are not necessary for this process. Microinjecting total RNA from germ cells of TA-displaying heterozygous zebrafish can trigger TA in wild-type embryos and in their progeny, suggesting a model whereby mutant mRNAs in the germline trigger a TA response that can be epigenetically inherited. In sum, this previously unidentified mode of TEI reveals a means by which parental mutations can modulate the offspring's transcriptome.
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