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Direct m6A recognition by IMP1 underlays an alternative model of target selection for non-canonical methyl-readers

Nicastro, Giuseppe; Abis, Giancarlo; Klein, Pierre; Esteban-Serna, Sofia; Gallagher, Christopher; Chaves-Arquero, Belen; Cai, Yuyang; ... Ramos, Andres; + view all (2023) Direct m6A recognition by IMP1 underlays an alternative model of target selection for non-canonical methyl-readers. Nucleic Acids Research , Article gkad534. 10.1093/nar/gkad534. (In press). Green open access

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Abstract

m6A methylation provides an essential layer of regulation in organismal development, and is aberrant in a range of cancers and neuro-pathologies. The information encoded by m6A methylation is integrated into existing RNA regulatory networks by RNA binding proteins that recognise methylated sites, the m6A readers. m6A readers include a well-characterised class of dedicated proteins, the YTH proteins, as well as a broader group of multi-functional regulators where recognition of m6A is only partially understood. Molecular insight in this recognition is essential to build a mechanistic understanding of global m6A regulation. In this study, we show that the reader IMP1 recognises the m6A using a dedicated hydrophobic platform that assembles on the methyl moiety, creating a stable high-affinity interaction. This recognition is conserved across evolution and independent from the underlying sequence context but is layered upon the strong sequence specificity of IMP1 for GGAC RNA. This leads us to propose a concept for m6A regulation where methylation plays a context-dependent role in the recognition of selected IMP1 targets that is dependent on the cellular concentration of available IMP1, differing from that observed for the YTH proteins.

Type: Article
Title: Direct m6A recognition by IMP1 underlays an alternative model of target selection for non-canonical methyl-readers
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/nar/gkad534
Publisher version: https://doi.org/10.1093/nar/gkad534
Language: English
Additional information: © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. © The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10172769
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