ArticleCell chemical biology2022
Splicing modulators elicit global translational repression by condensate-prone proteins translated from introns.
Article in Cell chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Halting translation by the letter with sequence-selective small molecules.Nature chemical biology · 2026Review
- Spirocyclic β-lactone secondary metabolites modulate spliceosome function.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Direct and indirect effects of spliceosome disruption compromise gene regulation by nonsense-mediated mRNA decay.RNA biology · 2025Article
- Coordinated expression of retained introns and poison exons in renal cell carcinoma.Cell reports · 2025Article
- Advances in ribosome profiling technologies.Biochemical Society transactions · 2025Review
- Girolline is a sequence context-selective modulator of eIF5A activity.Nature communications · 2025Article
- DMDA-PatA mediates RNA sequence-selective translation repression by anchoring eIF4A and DDX3 to GNG motifs.Nature communications · 2024Article
- Calibrated ribosome profiling assesses the dynamics of ribosomal flux on transcripts.Nature communications · 2024Article
- SARS-CoV-2 N protein-induced Dicer, XPO5, SRSF3, and hnRNPA3 downregulation causes pneumonia.Nature communications · 2024Article
- MOS4-associated complex contributes to proper splicing and suppression of ER stress under long-term heat stress in Arabidopsis.PNAS nexus · 2023Article
- A Truncated Form of the p27 Cyclin-Dependent Kinase Inhibitor Translated from Pre-mRNA Causes GMolecular and cellular biology · 2022Article
- Filter trapping protocol to detect aggregated proteins in human cell lines.STAR protocols · 2022Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Chemical splicing modulators that bind to the spliceosome have provided an attractive avenue for cancer treatment. Splicing modulators induce accumulation and subsequent translation of a subset of intron-retained mRNAs. However, the biological effect of proteins containing translated intron sequences remains unclear. Here, we identify a number of truncated proteins generated upon treatment with the splicing modulator spliceostatin A (SSA) via genome-wide ribosome profiling and bio-orthogonal noncanonical amino acid tagging (BONCAT) mass spectrometry. A subset of these truncated proteins has intrinsically disordered regions, forms insoluble cellular condensates, and triggers the proteotoxic stress response through c-Jun N-terminal kinase (JNK) phosphorylation, thereby inhibiting the mTORC1 pathway. In turn, this reduces global translation. These findings indicate that creating an overburden of condensate-prone proteins derived from introns represses translation and prevents further production of harmful truncated proteins. This mechanism appears to contribute to the antiproliferative and proapoptotic activity of splicing modulators.
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