Arid5a uses disordered extensions of its core ARID domain for distinct DNA- and RNA-recognition and gene regulation

von Ehr, Julian; Oberstrass, Lasse; Yazgan, Ege; Schnaubelt, Lara Ina; Blümel, Nicole; McNicoll, Francois; Weigand, Julia E.; Zarnack, Kathi; Müller-McNicoll, Michaela; Korn, Sophie Marianne; Schlundt, Andreas

doi:10.1016/j.jbc.2024.107457

Journal of Biological Chemistry

2024

DOI: 10.1016/j.jbc.2024.107457

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Arid5a uses disordered extensions of its core ARID domain for distinct DNA- and RNA-recognition and gene regulation

Julian von Ehr,

Lasse Oberstrass,

Ege Yazgan

et al.

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A core network in the SARS-CoV-2 nucleocapsid NTD mediates structural integrity and selective RNA-binding

Dhamotharan,

Korn,

Wacker

et al. 2024

Nat Commun

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The SARS-CoV-2 nucleocapsid protein is indispensable for viral RNA genome processing. Although the N-terminal domain (NTD) is suggested to mediate specific RNA-interactions, high-resolution structures with viral RNA are still lacking. Available hybrid structures of the NTD with ssRNA and dsRNA provide valuable insights; however, the precise mechanism of complex formation remains elusive. Similarly, the molecular impact of nucleocapsid NTD mutations that have emerged since 2019 has not yet been fully explored. Using crystallography and solution NMR, we investigate how NTD mutations influence structural integrity and RNA-binding. We find that both features rely on a core network of residues conserved in Betacoronaviruses, crucial for protein stability and communication among flexible loop-regions that facilitate RNA-recognition. Our comprehensive structural analysis demonstrates that contacts within this network guide selective RNA-interactions. We propose that the core network renders the NTD evolutionarily robust in stability and plasticity for its versatile RNA processing roles.

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A core network in the SARS-CoV-2 nucleocapsid NTD mediates structural integrity and selective RNA-binding

Dhamotharan,

Korn,

Wacker

et al. 2024

Nat Commun

View full text Add to dashboard Cite

show abstract

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Arid5a uses disordered extensions of its core ARID domain for distinct DNA- and RNA-recognition and gene regulation

Cited by 1 publication

References 88 publications

A core network in the SARS-CoV-2 nucleocapsid NTD mediates structural integrity and selective RNA-binding

A core network in the SARS-CoV-2 nucleocapsid NTD mediates structural integrity and selective RNA-binding

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