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Müller-Hermes, C. ; Piomponi, V.* ; Hilber, S.* ; Asami, S.* ; Kreutz, C.* ; Bussi, G.* ; Sattler, M.

Unique conformational dynamics and protein recognition of A-to-I hyper-edited dsRNA.

Nucleic Acids Res. 53:gkaf550 (2025)
Publ. Version/Full Text DOI PMC
Open Access Gold
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Adenosine-to-inosine (A-to-I) editing is a highly abundant modification of double-stranded RNA (dsRNA) and plays an important role in posttranscriptional gene regulation. Editing of multiple inosines by the ADAR1 enzyme leads to A-to-I hyper-editing of non-coding dsRNA, such as 3'UTRs, transposable elements, or foreign pathogenic RNAs, and is implicated in immune response and human diseases including cancer. The structural consequences of hyper-editing and its role in protein binding are poorly understood. Here, we combine solution nuclear magnetic resonance spectroscopy (NMR), biophysical methods such as small-angle X-ray scattering, and molecular dynamics simulations to study the sequence-dependent effects on conformation and dynamics of A-to-I hyper-editing for a 20-mer dsRNA and recognition of such RNAs by Endonuclease V. By comparing non-edited, single-edited, and hyper-edited dsRNA, we identify unique conformational features and extensive dynamics associated with hyper-editing, resulting in significantly increased base-pair opening. Hyper-edited dsRNA is more extended and adopts a highly dynamic ensemble of canonical and non-canonical conformations, which lead to preferential binding by Endonuclease V. Our integrated experimental and computational analysis identifies unique structural and dynamic features that are likely linked to specific protein recognition and the unique biological consequences of hyper-editing.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 0305-1048
e-ISSN 1362-4962
Journal Nucleic Acids Research
Quellenangaben Volume: 53, Issue: 12, Pages: , Article Number: gkaf550 Supplement: ,
Publisher Oxford University Press
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Structural Biology (STB)
Grants Institution, German DEAL
TUM Innovation Network
BMBF Cluster4Future program