دورية أكاديمية
أعرض في EDS

UPF1 helicase orchestrates mutually exclusive interactions with the SMG6 endonuclease and UPF2.

التفاصيل البيبلوغرافية
العنوان: UPF1 helicase orchestrates mutually exclusive interactions with the SMG6 endonuclease and UPF2.
المؤلفون: Langer LM; Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Martinsried/Munich D-82152, Germany., Kurscheidt K; Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Martinsried/Munich D-82152, Germany., Basquin J; Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Martinsried/Munich D-82152, Germany., Bonneau F; Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Martinsried/Munich D-82152, Germany., Iermak I; Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Martinsried/Munich D-82152, Germany., Basquin C; Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Martinsried/Munich D-82152, Germany., Conti E; Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Martinsried/Munich D-82152, Germany.
المصدر: Nucleic acids research [Nucleic Acids Res] 2024 Jun 10; Vol. 52 (10), pp. 6036-6048.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
أسماء مطبوعة: Publication: 1992- : Oxford : Oxford University Press
Original Publication: London, Information Retrieval ltd.
مواضيع طبية MeSH: Endonucleases*/metabolism , Endonucleases*/genetics , Nonsense Mediated mRNA Decay* , RNA Helicases*/metabolism , RNA Helicases*/genetics , RNA Helicases*/chemistry , RNA-Binding Proteins*/metabolism , RNA-Binding Proteins*/genetics , RNA-Binding Proteins*/chemistry , Trans-Activators*/metabolism , Trans-Activators*/genetics , Trans-Activators*/chemistry, Humans ; Cryoelectron Microscopy ; Endoribonucleases ; Models, Molecular ; Protein Binding ; RNA, Messenger/metabolism ; RNA, Messenger/genetics ; Transcription Factors/metabolism ; Transcription Factors/genetics ; RNA-Binding Motifs
مستخلص: Nonsense-mediated mRNA decay (NMD) is a conserved co-translational mRNA surveillance and turnover pathway across eukaryotes. NMD has a central role in degrading defective mRNAs and also regulates the stability of a significant portion of the transcriptome. The pathway is organized around UPF1, an RNA helicase that can interact with several NMD-specific factors. In human cells, degradation of the targeted mRNAs begins with a cleavage event that requires the recruitment of the SMG6 endonuclease to UPF1. Previous studies have identified functional links between SMG6 and UPF1, but the underlying molecular mechanisms have remained elusive. Here, we used mass spectrometry, structural biology and biochemical approaches to identify and characterize a conserved short linear motif in SMG6 that interacts with the cysteine/histidine-rich (CH) domain of UPF1. Unexpectedly, we found that the UPF1-SMG6 interaction is precluded when the UPF1 CH domain is engaged with another NMD factor, UPF2. Based on cryo-EM data, we propose that the formation of distinct SMG6-containing and UPF2-containing NMD complexes may be dictated by different conformational states connected to the RNA-binding status of UPF1. Our findings rationalize a key event in metazoan NMD and advance our understanding of mechanisms regulating activity and guiding substrate recognition by the SMG6 endonuclease.
(© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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معلومات مُعتمدة: Max Planck Gesellschaft; 101054447 European Research Council Advanced Investigator Grant GOVERNA; DFG SFB1035 Deutsche Forschungsgemeinschaft; Boehringer Ingelheim Fonds
المشرفين على المادة: EC 3.1.- (Endonucleases)
EC 3.1.- (Endoribonucleases)
EC 3.6.4.13 (RNA Helicases)
0 (RNA, Messenger)
0 (RNA-Binding Proteins)
EC 3.1.- (SMG6 protein, human)
0 (Trans-Activators)
0 (Transcription Factors)
EC 3.6.4.13 (UPF1 protein, human)
0 (UPF2 protein, human)
تواريخ الأحداث: Date Created: 20240506 Date Completed: 20240609 Latest Revision: 20240611
رمز التحديث: 20240611
مُعرف محوري في PubMed: PMC11162806
DOI: 10.1093/nar/gkae323
PMID: 38709891
قاعدة البيانات: MEDLINE
الوصف
تدمد:1362-4962
DOI:10.1093/nar/gkae323