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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)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
ISSN (print) / ISBN 0305-1048
e-ISSN 1362-4962
Zeitschrift Nucleic Acids Research
Quellenangaben Band: 53, Heft: 12, Seiten: , Artikelnummer: gkaf550 Supplement: ,
Verlag Oxford University Press
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Structural Biology (STB)
Förderungen Institution, German DEAL
TUM Innovation Network
BMBF Cluster4Future program