TUG1 supports mouse two-cell-stage development and ZGA-associated transcription through MAPK8 signaling
TL;DR
It is demonstrated that TUG1, which is highly expressed in tumors, regulates early embryonic development in mice and is transformed 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.
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.