ArticleNucleic acids research2023
NOVA1 prevents overactivation of the unfolded protein response and facilitates chromatin access during human white adipogenesis.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- Exploration of Conserved Human Adipose Subpopulations Using Targeted Single-Nuclei RNA Sequencing Data Sets.Journal of the American Heart Association · 2025Article
- Single-cell transcriptomics of clinical grade adipose-derived regenerative cells reveals consistency between donors independent of gender and BMI.Stem cell research & therapy · 2025Article
- A humanized NOVA1 splicing factor alters mouse vocal communications.Nature communications · 2025Article
- The splicing machinery is dysregulated and represents a therapeutic vulnerability in breast cancer.Cellular and molecular life sciences : CMLS · 2024Article
- Interaction of theCells · 2023Article
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The molecular mechanism underlying white adipogenesis in humans has not been fully elucidated beyond the transcriptional level. Here, we found that the RNA-binding protein NOVA1 is required for the adipogenic differentiation of human mesenchymal stem cells. By thoroughly exploring the interactions between NOVA1 and its binding RNA, we proved that NOVA1 deficiency resulted in the aberrant splicing of DNAJC10 with an in-frame premature stop codon, reduced DNAJC10 expression at the protein level and hyperactivation of the unfolded protein response (UPR). Moreover, NOVA1 knockdown abrogated the down-regulation of NCOR2 during adipogenesis and up-regulated the 47b+ splicing isoform, which led to decreased chromatin accessibility at the loci of lipid metabolism genes. Interestingly, these effects on human adipogenesis could not be recapitulated in mice. Further analysis of multispecies genomes and transcriptomes indicated that NOVA1-targeted RNA splicing is evolutionarily regulated. Our findings provide evidence for human-specific roles of NOVA1 in coordinating splicing and cell organelle functions during white adipogenesis.
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Registered trials
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