Maternal TDP43 orchestrates nuclear speckle assembly and zygotic splicing activation during oocyte-to-embryo transition in mice.

ABSTRACT: Zygotic splicing activation (ZSA) is a crucial process of mRNA post-transcriptional regulation during maternal-to-zygotic transition, ensuring normal embryonic development. However, the key factors and mechanisms underlying ZSA regulation remain unclear. We observed that the nuclear speckle (NS), a key splicing region, was newly established at the 2-cell stage in mice and was consistent with the ZSA period. Moreover, NS and TAR DNA-binding protein-43 (TDP43) always exhibited a partially adjacent and mutually exclusive localization relationship. TDP43 performed its function through liquid-liquid phase separation. The condensation-deficient state of TDP43 was the active form involved in NS regulation in 2-cell embryos. Additionally, TDP43 could also interact with both transcribed RNAs associ

SUBMITTER: Deng ZQ 

PROVIDER: S-EPMC12784972 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature