2. Academic Validation
  3. Zygotic Splicing Activation of the Transcriptome is a Crucial Aspect of Maternal-to-Zygotic Transition and Required for the Conversion from Totipotency to Pluripotency

Zygotic Splicing Activation of the Transcriptome is a Crucial Aspect of Maternal-to-Zygotic Transition and Required for the Conversion from Totipotency to Pluripotency

  • Adv Sci (Weinh). 2024 Feb 2:e2308496. doi: 10.1002/advs.202308496.
Hua Zhang 1 2,  Yang Wang 3,  Zhe-Wei Hu 1,  Yun-Wen Wu 3,  Nuo Chen 3,  Yi-Min Zhu 4,  Yuan-Song Yu 5,  Heng-Yu Fan 3 6 7,  Hua-Nan Wang 1 2
Affiliations

Affiliations

  • 1 MOA Key Laboratory of Animal Virology, Center for Veterinary Sciences, Zhejiang University, Hangzhou, 310058, China.
  • 2 Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China.
  • 3 MOE Key Laboratory for Biosystems Homeostasis and Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China.
  • 4 Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310002, China.
  • 5 Savaid Stomatology School, Hangzhou Medical College, Hangzhou, 310053, China.
  • 6 Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China.
  • 7 Center for Biomedical Research, Shaoxing Institute, Zhejiang University, Shaoxing, 312000, China.
PMID: 38308190 DOI: 10.1002/advs.202308496
Abstract

During maternal-to-zygotic transition (MZT) in the embryo, mRNA undergoes complex post-transcriptional regulatory processes. However, it is unclear whether and how alternative splicing plays a functional role in MZT. By analyzing transcriptome changes in mouse and human early embryos, dynamic changes in alternative splicing during MZT are observed and a previously unnoticed process of zygotic splicing activation (ZSA) following embryonic transcriptional activation is described. As the underlying mechanism of RNA splicing, splicing factors undergo dramatic maternal-to-zygotic conversion. This conversion relies on the key maternal factors BTG4 and PABPN1L and is zygotic-transcription-dependent. CDK11-dependent phosphorylation of the key splicing factor, SF3B1, and its aggregation with SRSF2 in the subnuclear domains of 2-cell embryos are prerequisites for ZSA. Isoforms generated by erroneous splicing, such as full-length Dppa4, hinder normal embryonic development. Moreover, alternative splicing regulates the conversion of early embryonic blastomeres from totipotency to pluripotency, thereby affecting embryonic lineage differentiation. ZSA is an essential post-transcriptional process of MZT and has physiological significance in generating new life. In addition to transcriptional activation, appropriate expression of transcript isoforms is also necessary for preimplantation embryonic development.

Keywords

RNA processing; alternative splicing; early embryo; splicing factors; totipotency and pluripotency; zygotic genome activation.

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