Direct and indirect effects of spliceosome disruption compromise gene regulation by Nonsense-Mediated mRNA Decay
2024

Effects of Spliceosome Disruption on Gene Regulation

Sample size: 18 publication Evidence: moderate

Author Information

Author(s): Caleb M. Embree, Andreas Stephanou, Guramrit Singh

Primary Institution: Cold Spring Harbor Laboratory

Hypothesis

Does spliceosome disruption lead to upregulation of NMD targets?

Conclusion

Spliceosome disruption upregulates a broad set of NMD targets, potentially contributing to cellular dysfunction.

Supporting Evidence

  • Spliceosome disruption leads to upregulation of NMD targeted mRNA isoforms.
  • Four spliceosome proteins may have a direct role in NMD.
  • Transcriptome alterations are observed in cells treated with spliceosome inhibitors.
  • Similar effects are seen in cells from retinitis pigmentosa patients.

Takeaway

When the spliceosome, a machine that helps make RNA, doesn't work right, it can cause problems in how genes are controlled.

Methodology

Analysis of RNA-seq datasets from K562 and HepG2 cells depleted of spliceosome components.

Participant Demographics

K562 and HepG2 cell lines.

Digital Object Identifier (DOI)

10.1101/2024.12.27.630533

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