ArticleNucleic acids research2010
The ribosome assembly factor Nep1 responsible for Bowen-Conradi syndrome is a pseudouridine-N1-specific methyltransferase.
Article in Nucleic acids research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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78 citing papers in PubMed.
- Illuminating ribosome biogenesis disorders through structural biology.RNA biology · 2026Review
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- A comprehensive analysis of the use of nucleoside analogues in RNA therapeutics.Journal of translational medicine · 2026Review
- Enzyme-mediated alkynylation enables transcriptome-wide identification of pseudouridine modifications.Nature communications · 2026Article
- Ribosomal modifications are associated with mesenchymal fate selection in the neural crest lineage.Nature communications · 2026Article
- Seven wonders of RNA modification biology.RNA (New York, N.Y.) · 2026Review
- Accelerate the Highly Efficient Development of mRNA Vaccines Through Advanced Computational Methods.MedComm · 2026Review
- Advances in Quantitative Techniques for Mapping RNA Modifications.Life (Basel, Switzerland) · 2025Review
- Manipulation of Nuclear-Related Pathways During Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication.Viruses · 2025Review
- Mechanistic Insights into SAM-Dependent Methyltransferases: A Review of Computational Approaches.International journal of molecular sciences · 2025Review
- Mechanisms of ribosomopathy and phase separation-related ribosomopathy.Journal of Zhejiang University. Science. B · 2025Review
- Specialized ribosomes: integrating new insights and current challenges.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Structures of Saccharolobus solfataricus initiation complexes with leaderless mRNAs highlight archaeal features and eukaryotic proximity.Nature communications · 2025Article
- Protein-small molecule binding site prediction based on a pre-trained protein language model with contrastive learning.Journal of cheminformatics · 2024Article
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- Pseudouridine andRSC chemical biology · 2024Review
- Landscape of RNA pseudouridylation in archaeon Sulfolobus islandicus.Nucleic acids research · 2024Article
- Tailor made: the art of therapeutic mRNA design.Nature reviews. Drug discovery · 2024Review
- The antiproliferative effect of FGF2 in K-Ras-driven tumor cells involves modulation of rRNA and the nucleolus.Journal of cell science · 2023Article
18 more citing papers are in PubMed but not listed here.
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11 authors.
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Abstract
Nep1 (Emg1) is a highly conserved nucleolar protein with an essential function in ribosome biogenesis. A mutation in the human Nep1 homolog causes Bowen-Conradi syndrome-a severe developmental disorder. Structures of Nep1 revealed a dimer with a fold similar to the SPOUT-class of RNA-methyltransferases suggesting that Nep1 acts as a methyltransferase in ribosome biogenesis. The target for this putative methyltransferase activity has not been identified yet. We characterized the RNA-binding specificity of Methanocaldococcus jannaschii Nep1 by fluorescence- and NMR-spectroscopy as well as by yeast three-hybrid screening. Nep1 binds with high affinity to short RNA oligonucleotides corresponding to nt 910-921 of M. jannaschii 16S rRNA through a highly conserved basic surface cleft along the dimer interface. Nep1 only methylates RNAs containing a pseudouridine at a position corresponding to a previously identified hypermodified N1-methyl-N3-(3-amino-3-carboxypropyl) pseudouridine (m1acp3-Psi) in eukaryotic 18S rRNAs. Analysis of the methylated nucleoside by MALDI-mass spectrometry, HPLC and NMR shows that the methyl group is transferred to the N1 of the pseudouridine. Thus, Nep1 is the first identified example of an N1-specific pseudouridine methyltransferase. This enzymatic activity is also conserved in human Nep1 suggesting that Nep1 is the methyltransferase in the biosynthesis of m1acp3-Psi in eukaryotic 18S rRNAs.
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