Nucleolus assembly impairment leads to two-cell transcriptional repression via NPM1-mediated PRC2 recruitment.
Dingfeng LiRan CaoQiaodan LiYang YangAihui TangJuan ZhangQiang LiuPublished in: Nature structural & molecular biology (2023)
The nucleolus is a compartmentalized organelle in eukaryotic cells known to form during embryogenesis, yet how its layered architecture is transformed from homogenous precursor bodies is unclear, and any impacts of this formation on embryonic cell fate determination remain unknown. Here, we demonstrate that lncRNA LoNA tethers granular-component-enriched NPM1 to dense-fibrillar-component-enriched FBL and drives the formation of compartmentalized nucleolus via facilitating liquid-liquid phase separation of those two nucleolar proteins. Phenotypically, LoNA-deficient embryos show developmental arrest at the two-cell (2C) stage. Mechanistically, we demonstrate that LoNA deficiency leads to nucleolar formation failure, resulting in mislocalization and acetylation of NPM1 in the nucleoplasm. Acetylated NPM1 recruits and guides PRC2 complex to 2C genes, where PRC2 complex trimethylates H3K27, leading to transcriptional repression of these genes. Collectively, our findings reveal that lncRNA is required for the establishment of nucleolar structure, and this process has an impact on two-cell embryonic development via 2C transcriptional activation.
Keyphrases
- acute myeloid leukemia
- single cell
- gene expression
- genome wide
- cell therapy
- transcription factor
- long non coding rna
- cell fate
- dna methylation
- genome wide identification
- oxidative stress
- induced apoptosis
- mass spectrometry
- bone marrow
- mesenchymal stem cells
- simultaneous determination
- solid phase extraction
- heat shock protein