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  Parental mutations influence wild-type offspring via transcriptional adaptation

Jiang, Z., El-Brolosy, M. A., Serobyan, V., Welker, J. M., Retzer, N., Dooley, C. M., et al. (2022). Parental mutations influence wild-type offspring via transcriptional adaptation. SCIENCE ADVANCES, 8(47): eabj2029. doi:10.1126/sciadv.abj2029.

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 Creators:
Jiang, Zhen1, Author           
El-Brolosy, Mohamed A.1, Author           
Serobyan, Vahan1, 2, Author           
Welker, Jordan M.1, Author           
Retzer, Nicholas1, Author           
Dooley, Christopher M.1, 3, Author           
Jakutis, Gabrielius1, Author           
Juan, Thomas1, Author
Fukuda, Nana1, Author           
Maischein, Hans-Martin1, 3, 4, Author           
Balciunas, Darius, Author
Stainier, Didier Y. R.1, Author           
Affiliations:
1Developmental Genetics, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591697              
2Department Integrative Evolutionary Biology, Max Planck Institute for Developmental Biology, Max Planck Society, ou_3375786              
3Department Genetics, Max Planck Institute for Developmental Biology, Max Planck Society, ou_3375716              
4Research Group Colour Pattern Formation, Max Planck Institute for Developmental Biology, Max Planck Society, ou_3489217              

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 Abstract: 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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 Dates: 2022-11-25
 Publication Status: Published online
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 Identifiers: ISI: 000968162100001
DOI: 10.1126/sciadv.abj2029
PMID: 36427314
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Title: SCIENCE ADVANCES
Source Genre: Journal
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Pages: - Volume / Issue: 8 (47) Sequence Number: eabj2029 Start / End Page: - Identifier: ISSN: 2375-2548