Chromatin-associated lncRNA-splicing factor condensates regulate hypoxia responsive RNA processing of genes pre-positioned near nuclear speckles
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View abstract on PubMed
Summary
This summary is machine-generated.Hypoxia triggers alternative splicing (AS) via MALAT1 lncRNA, which organizes splicing factors near nuclear speckles. This spatial regulation controls gene expression during cellular stress.
Area Of Science
- Molecular Biology
- Cell Biology
- Genomics
Background
- Alternative splicing (AS) is crucial for tumor progression and metastasis.
- The role of nuclear organization and long noncoding RNAs in hypoxia-induced AS is largely unknown.
Purpose Of The Study
- To investigate how higher-order genome and nuclear domain organizations control hypoxia-induced alternative splicing.
- To elucidate the role of MALAT1 long noncoding RNA in regulating hypoxia-responsive AS.
Main Methods
- Observation of gene positioning relative to nuclear speckles (NS).
- Analysis of MALAT1 long noncoding RNA induction and function under hypoxia.
- Investigation of SRSF1 splicing factor organization and binding dynamics.
Main Results
- Hypoxia-responsive genes localize near nuclear speckles (NS).
- MALAT1, induced by hypoxia, organizes SRSF1 splicing factors near NS.
- MALAT1 promotes SRSF1 recruitment to pre-mRNAs via phase-separated condensates, enhancing AS.
Conclusions
- MALAT1 plays a critical role in spatially organizing alternative splicing under hypoxia.
- MALAT1-mediated SRSF1 condensate formation is key for regulating AS efficiency during cellular stress.
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