Perturbing nuclear glycosylation in the mouse preimplantation embryo slows down embryonic development

• 成果类型: Article
• 署名作者: Formichetti, Sara; Serrano, Joana B.; Chitnavis, Urvashi; Sadowska, Agnieszka; Liu, Na; Boskovic, Ana; Boulard, Matthieu
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13145
• DOI: 10.1073/pnas.2410520122
• 发表日期: 2025-04-15
• 关键词: o-glcnac transferase; n-acetylglucosamine; cytosolic proteins; x-chromosome; cell-growth; rna-seq; mitochondrial; gene; identification; chromatin

摘要

The main form of intracellular protein glycosylation (O-GlcNAc) is reversible and has been mapped on thousands of cytoplasmic and nuclear proteins, including RNA polymerase II, transcription factors, and chromatin modifiers. The O-GlcNAc modification is catalyzed by a single enzyme known as O-GlcNAc Transferase, that is required for mammalian early development. Yet, neither the regulatory function of protein O-GlcNAcylation in the embryo nor the embryonic O-GlcNAc proteome have been documented. Here, we devised a strategy to enzymatically remove O-GlcNAc from pre-implantation embryonic nuclei, where this modification accumulates coincidently with embryonic genome activation (EGA). Unexpectedly, the depletion of nuclear O-GlcNAc to undetectable levels has no impact on EGA, but dampens the transcriptional upregulation of the translational machinery, and triggers a spindle checkpoint response. These molecular alterations were phenotypically associated with a developmental delay starting from early cleavage stages and persisting after embryo implantation, establishing a link between nuclear glycosylation and the pace of embryonic development.