Omics · study · 2026
NEAT1 structural remodeling rewires MYC degradation pathway [RNA_seq_NEAT1_gapmer]
Listed in NCBI GEO
The MYC is a oncogenic driver in diverse human cancers.
Description
However, its intrinsically disordered structure has precluded direct pharmacological inhibition, posing a major challenge to targeting MYC-driven malignancies. This limitation has prompted the search for alternative strategies to modulate MYC activity.
Recent findings suggest that MYC engage with cellular RNAs, revealing a previously underappreciated layer of regulatory control. Here, we identify the long noncoding RNA NEAT1_1 as a component of a MYC–NEAT1_1 protein–RNA complex that modulates MYC protein stability. While NEAT1 knockdown moderately increases MYC levels, we hypothesized that its structural conformation is critical to this regulatory function.
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To test this, we designed 88 antisense oligonucleotide mixmers targeting distinct structural regions of NEAT1_1. This screen uncovered both MYC-destabilizing and MYC-stabilizing oligonucleotides, without altering NEAT1_1 expression levels. A focused CRISPR screen identified UBR5 as an E3 ligase required for MYC-destabilizing mixmers induced MYC degradation, and we validated that these mixmers enhanced the MYC–UBR5 interaction, leading to more polyubiquitination of MYC.
Our findings highlight a structure-guided mechanism by which a scaffold lncRNA governs the stability of an otherwise undruggable oncogene. This study provides proof-of-concept that RNA structural modulation can rewire protein turnover pathways, offering a promising therapeutic avenue for MYC-driven cancers.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE309nnn/GSE309556 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE309556 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1336249 ncbi.nlm.nih.gov/bioproject/PRJNA1336249 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE309556 | 11 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | 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 |