TPST2-mediated tyrosine sulfation orchestrates porcine preimplantation development

BACKGROUND: Tyrosine sulfation is a widespread posttranslational modification in mammals and is known to influence protein function and signaling. However, its functional significance during porcine preimplantation development remains poorly understood. RESULTS: In this study, we demonstrate that TPST2-mediated tyrosine sulfation is critical for early porcine embryonic development. TPST2 is transcriptionally activated during zygotic genome activation by its antisense long noncoding RNA, termed aTPST2, which recruits MED4, a core subunit of the Mediator complex, to activate TPST2 transcription in cis. Mechanistically, TPST2 mediates sulfation at tyrosine 39 (Y39) of TTYH3, enhancing its protein stability. The stabilized TTYH3 interacts with RAP1B to activate MAPK signaling, thereby ensuring proper embryonic development. CONCLUSIONS: Our findings elucidate a compelling molecular mechanism by which tyrosine sulfation orchestrates porcine preimplantation development. Together, these results provide new insights into the developmental functions of tyrosine sulfation.