Omics · study · 2026
Nuclear envelope rupture causes RNA polymerase loss in LMNA cardiomyopathy
Listed in NCBI GEO
Localized rupture of the nuclear envelope has been reported in various pathologies, including cancer, neurodegenerative disease, myocardial infarction, as well as dilated cardiomyopathy caused by Lamin A/C gene mutations (LMNA-DCM).
Description
Whether and how nuclear rupture contributes to disease remains unclear. Here, we report that nuclear rupture causes global transcriptional deficiency in a mouse model of LMNA-DCM.
We observed that ruptured nuclei lost chromatin-bound RNA polymerase II, leading to downregulation of numerous genes essential for cardiomyocyte structure and function. Notably, over one third of ruptured nuclei resealed and regained transcription. Resealing involved the ESCRT-III membrane remodeling complex and was cardioprotective, as its blockade increased rupture frequency and accelerated cardiomyopathy.
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However, resealing was ineffective: resealed nuclei re-ruptured at twice the resealing rate and ten-fold faster than the de novo rupture rate. A mathematical model predicted a steady accumulation of ruptured nuclei despite ongoing resealing. Consistently, a human LMNA-mutant heart contained numerous ruptured nuclei at the time of disease presentation.
These findings link nuclear rupture to organ deterioration through global transcriptional deficiency and suggested rupture repair as a critical modifier of nuclear rupture-associated conditions.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE325nnn/GSE325163 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325163 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1438739 ncbi.nlm.nih.gov/bioproject/PRJNA1438739 ↗
project · from NCBI GEO
Topics
- Stated by source
- Genome binding/occupancy profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75% · Cardiomyopathy 75% · Disease 75% · Heart 75% · Myocardial infarction 75%
Provenance · 1 source records, 12 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE325163 | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[anatomy].local:anatomy:heart | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[disease].local:disease:cardiomyopathy | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[disease].local:disease:myocardial-infarction | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:genome-binding-occupancy-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |