TUG1 supports mouse two-cell-stage development and ZGA-associated transcription through MAPK8 signaling
- 1Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University, Harbin, 150030 P. R. China
Abstract
Cancer cells possess unlimited proliferative potential, and the high expression of lncRNAs widely promotes cancer progression. Mammalian early embryos share similar characteristics, where numerous endogenous retroviruses become transcriptionally active during zygotic genome activation (ZGA). However, whether cancer-promoting lncRNAs can also facilitate early embryonic development remains unclear. In this study, we demonstrated that TUG1, which is highly expressed in tumors, regulates early embryonic development in mice. TUG1 deficiency results in the arrest of mouse embryos at the two-cell stage, accompanied by disruption of the MAPK signaling pathway, and consequently leads to the failure of ZGA. Mechanistically, we uncover a TUG1-hnRNPA1 ribonucleoprotein complex that actively licenses ZGA by promoting the transcription of MAPK8, thereby activating the essential MAPK signaling pathway. This study transforms our understanding of TUG1 from a cancer-specific effector to a critical regulator of the ZGA, raising the possibility that related regulatory principles may operate in other biological contexts.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00018-026-06374-z.
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BibTeX
@article{wang2026tug1,
title = {{TUG1 supports mouse two-cell-stage development and ZGA-associated transcription through MAPK8 signaling}},
author = {Jianwu Wang and Guang Yang and Qingbo Yang and Hongshuang Xie and Yiwei Zhang and Jiaqiang Wang},
journal = {Cellular and Molecular Life Sciences: CMLS},
year = {2026},
month = aug,
doi = {10.1007/s00018-026-06374-z},
url = {https://doi.org/10.1007/s00018-026-06374-z},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - TUG1 supports mouse two-cell-stage development and ZGA-associated transcription through MAPK8 signaling
AU - Jianwu Wang
AU - Guang Yang
AU - Qingbo Yang
AU - Hongshuang Xie
AU - Yiwei Zhang
AU - Jiaqiang Wang
PY - 2026
DA - 2026/08/11
JO - Cellular and Molecular Life Sciences: CMLS
DO - 10.1007/s00018-026-06374-z
UR - https://doi.org/10.1007/s00018-026-06374-z
AB - Cancer cells possess unlimited proliferative potential, and the high expression of lncRNAs widely promotes cancer progression. Mammalian early embryos share similar characteristics, where numerous endogenous retroviruses become transcriptionally active during zygotic genome activation (ZGA). However, whether cancer-promoting lncRNAs can also facilitate early embryonic development remains unclear. In this study, we demonstrated that TUG1, which is highly expressed in tumors, regulates early embryonic development in mice. TUG1 deficiency results in the arrest of mouse embryos at the two-cell stage, accompanied by disruption of the MAPK signaling pathway, and consequently leads to the failure of ZGA. Mechanistically, we uncover a TUG1-hnRNPA1 ribonucleoprotein complex that actively licenses ZGA by promoting the transcription of MAPK8, thereby activating the essential MAPK signaling pathway. This study transforms our understanding of TUG1 from a cancer-specific effector to a critical regulator of the ZGA, raising the possibility that related regulatory principles may operate in other biological contexts. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00018-026-06374-z.
SN - 1420-682X
SN - 1420-9071
ER -