Endogenous retroviruses synthesize heterologous chimeric RNAs to reinforce human early embryo development
Zygotic genome activation (ZGA) failure leads to developmental arrest and poses a clinical challenge to women's fertility. We observed that human embryos arresting at the eight-cell ZGA stage exhibited specific down-regulation of endogenous retrovirus MLT2A1. Depleting MLT2A1 resulted in a failure in embryo development and a reduction in ZGA gene expression. Mechanistically, MLT2A1s synthesized chimeric transcripts with downstream coding and noncoding sequences, predominantly with heterologous retro-transposable elements. These diverse fusion sequences expanded the genome-targeting spectrum of MLT2A1 RNAs. Nevertheless, the shared MLT2A1 sequences partnered with heterogeneous nuclear ribonucleoprotein U (HNRNPU) to recruit RNA polymerase II, promoting global transcription of ZGA genes and autoamplification of the MLT2A1 subfamily. Thus, MLT2A1 chimeric RNAs formed an interlocking network that acts synergistically to boost human ZGA and early embryogenesis.
Authors
- You Wu (ORCID: https://orcid.org/0009-0000-9779-0309)
- Yangquan Xiang (ORCID: https://orcid.org/0000-0002-1368-4929)
- Yawei Gao (ORCID: https://orcid.org/0000-0001-8946-9697)
- Hong‐Qing Liang (ORCID: https://orcid.org/0000-0002-5239-5345)
- Yun-Shen Chan (ORCID: https://orcid.org/0000-0002-5697-3122)
- Shaorong Gao
- Jun Ma (ORCID: https://orcid.org/0000-0002-5510-6895)
- Wanlu Liu (ORCID: https://orcid.org/0000-0001-5963-2908)
- Zhipeng Ai (ORCID: https://orcid.org/0000-0002-2185-3534)
- Li Shen
- Jiabao Bu
- Yuli Qian
- Zhengyi Li
- Jiaxu Wang
- Fei Huang
- Ruonan Tian
- Dan Zhang
- Xijia Chen
- Danya Wu
Institutions
- Zhejiang International Studies University (CN)
- Guangzhou Experimental Station (CN)
- Ministry of Education (TH)
- Shanghai East Hospital (CN)
- Zhejiang Center for Disease Control and Prevention (CN)
- Shanghai First Maternity and Infant Hospital (CN)
- Second Affiliated Hospital of Zhejiang University (CN)
- Artificial Intelligence in Medicine (Canada) (CA)
- Genome Institute of Singapore (SG)
- Zhejiang University (CN)
Publication Details
- Journal
- Science
- Published
- 2026-01-22
- DOI
- https://doi.org/10.1126/science.adv5257
- Citations
- 2
- Primary Topic
- Chromosomal and Genetic Variations
- Type
- article
- Field-Weighted Citation Impact
- 62.68