ArticleProceedings of the National Academy of Sciences of the United States of America2020
Molecular basis of the selective processing of short mRNA substrates by the DcpS mRNA decapping enzyme.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Liquid-liquid phase separation and the formation of amyloid fibrils from DcpS scavenger enzymes.Scientific reports · 2026Article
- Functional characterization of human recessive DIS3 variants in premature ovarian insufficiency†.Biology of reproduction · 2025Article
- Cryo-EM structures of Thogoto virus polymerase reveal unique RNA transcription and replication mechanisms among orthomyxoviruses.Nature communications · 2024Article
- Protein Signatures of Parathyroid Adenoma according to Tumor Volume and Functionality.Endocrinology and metabolism (Seoul, Korea) · 2024Article
- Assessment of ferroptosis as a promising candidate for metastatic uveal melanoma treatment and prognostication.Frontiers in pharmacology · 2024Review
- Assessing the applicability ofJournal of biomolecular NMR · 2023Article
- Low Resource Integrated Platform for Production and Analysis of Capped mRNA.ACS synthetic biology · 2023Article
- Observation of conformational changes that underlie the catalytic cycle of Xrn2.Nature chemical biology · 2022Article
- Targeted Degradation of mRNA Decapping Enzyme DcpS by a VHL-Recruiting PROTAC.ACS chemical biology · 2022Article
- Substrate-Based Design of Cytosolic Nucleotidase IIIB Inhibitors and Structural Insights into Inhibition Mechanism.Pharmaceuticals (Basel, Switzerland) · 2022Article
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4 authors.
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Abstract
The 5' messenger RNA (mRNA) cap structure enhances translation and protects the transcript against exonucleolytic degradation. During mRNA turnover, this cap is removed from the mRNA. This decapping step is catalyzed by the Scavenger Decapping Enzyme (DcpS), in case the mRNA has been exonucleolyticly shortened from the 3' end by the exosome complex. Here, we show that DcpS only processes mRNA fragments that are shorter than three nucleotides in length. Based on a combination of methyl transverse relaxation optimized (TROSY) NMR spectroscopy and X-ray crystallography, we established that the DcpS substrate length-sensing mechanism is based on steric clashes between the enzyme and the third nucleotide of a capped mRNA. For longer mRNA substrates, these clashes prevent conformational changes in DcpS that are required for the formation of a catalytically competent active site. Point mutations that enlarge the space for the third nucleotide in the mRNA body enhance the activity of DcpS on longer mRNA species. We find that this mechanism to ensure that the enzyme is not active on translating long mRNAs is conserved from yeast to humans. Finally, we show that the products that the exosome releases after 3' to 5' degradation of the mRNA body are indeed short enough to be decapped by DcpS. Our data thus directly confirms the notion that mRNA products of the exosome are direct substrates for DcpS. In summary, we demonstrate a direct relationship between conformational changes and enzyme activity that is exploited to achieve substrate selectivity.
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