Systematic analysis of A-to-I RNA editing upon release of ADAR from the nucleolus

Adenosine-to-inosine (A-to-I) RNA editing, catalysed by two ADAR isoforms (p110 and p150) and ADARB1, is a critical regulatory step in gene expression. Intriguingly, the nucleolus is conspicuously rich in ADAR p110 and ADARB1, though the biological reason remains unclear. To investigate a putative r...

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Main Authors: Ruben Lattuca, Rümeyza Bascetin, Vincent Detours, Denis L. J. Lafontaine
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:RNA Biology
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Online Access:https://www.tandfonline.com/doi/10.1080/15476286.2025.2515655
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author Ruben Lattuca
Rümeyza Bascetin
Vincent Detours
Denis L. J. Lafontaine
author_facet Ruben Lattuca
Rümeyza Bascetin
Vincent Detours
Denis L. J. Lafontaine
author_sort Ruben Lattuca
collection DOAJ
description Adenosine-to-inosine (A-to-I) RNA editing, catalysed by two ADAR isoforms (p110 and p150) and ADARB1, is a critical regulatory step in gene expression. Intriguingly, the nucleolus is conspicuously rich in ADAR p110 and ADARB1, though the biological reason remains unclear. To investigate a putative role of nucleolar enrichment in ADAR, we released it gradually from the nucleolus into the nucleoplasm by treating cells briefly with low doses of actinomycin D, known to disassemble the nucleolus. Deep sequencing of the transcriptome revealed that as ADAR dissociated from the nucleolus, RNA editing increased significantly, with sharp rises in both the number of edited sites and editing frequency. This co-transcriptional editing, predominantly in intronic regions, was associated with disrupted pre-mRNA splicing, causing exon skipping and intron retention which remodelled gene expression. These findings suggest that the nucleolar localization of ADAR serves to restrain its activity, preventing excessive editing that could lead to splicing errors and cellular dysfunction.
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spelling doaj-art-e43f948ca03445c0b49ab1fb578276752025-08-20T03:16:31ZengTaylor & Francis GroupRNA Biology1547-62861555-85842025-12-0122111810.1080/15476286.2025.2515655Systematic analysis of A-to-I RNA editing upon release of ADAR from the nucleolusRuben Lattuca0Rümeyza Bascetin1Vincent Detours2Denis L. J. Lafontaine3RNA Molecular Biology, Fonds de la Recherche Scientifique (F.R.S./FNRS), Université libre de Bruxelles (ULB), Biopark campus, B-6041 Gosselies, BelgiumRNA Molecular Biology, Fonds de la Recherche Scientifique (F.R.S./FNRS), Université libre de Bruxelles (ULB), Biopark campus, B-6041 Gosselies, BelgiumIRIBHM Jacques E. Dumont, Université libre de Bruxelles, Lennik, BelgiumRNA Molecular Biology, Fonds de la Recherche Scientifique (F.R.S./FNRS), Université libre de Bruxelles (ULB), Biopark campus, B-6041 Gosselies, BelgiumAdenosine-to-inosine (A-to-I) RNA editing, catalysed by two ADAR isoforms (p110 and p150) and ADARB1, is a critical regulatory step in gene expression. Intriguingly, the nucleolus is conspicuously rich in ADAR p110 and ADARB1, though the biological reason remains unclear. To investigate a putative role of nucleolar enrichment in ADAR, we released it gradually from the nucleolus into the nucleoplasm by treating cells briefly with low doses of actinomycin D, known to disassemble the nucleolus. Deep sequencing of the transcriptome revealed that as ADAR dissociated from the nucleolus, RNA editing increased significantly, with sharp rises in both the number of edited sites and editing frequency. This co-transcriptional editing, predominantly in intronic regions, was associated with disrupted pre-mRNA splicing, causing exon skipping and intron retention which remodelled gene expression. These findings suggest that the nucleolar localization of ADAR serves to restrain its activity, preventing excessive editing that could lead to splicing errors and cellular dysfunction.https://www.tandfonline.com/doi/10.1080/15476286.2025.2515655A-to-I RNA editingADARnucleolusRNA modificationepitranscriptomicspre-mRNA splicing regulation
spellingShingle Ruben Lattuca
Rümeyza Bascetin
Vincent Detours
Denis L. J. Lafontaine
Systematic analysis of A-to-I RNA editing upon release of ADAR from the nucleolus
RNA Biology
A-to-I RNA editing
ADAR
nucleolus
RNA modification
epitranscriptomics
pre-mRNA splicing regulation
title Systematic analysis of A-to-I RNA editing upon release of ADAR from the nucleolus
title_full Systematic analysis of A-to-I RNA editing upon release of ADAR from the nucleolus
title_fullStr Systematic analysis of A-to-I RNA editing upon release of ADAR from the nucleolus
title_full_unstemmed Systematic analysis of A-to-I RNA editing upon release of ADAR from the nucleolus
title_short Systematic analysis of A-to-I RNA editing upon release of ADAR from the nucleolus
title_sort systematic analysis of a to i rna editing upon release of adar from the nucleolus
topic A-to-I RNA editing
ADAR
nucleolus
RNA modification
epitranscriptomics
pre-mRNA splicing regulation
url https://www.tandfonline.com/doi/10.1080/15476286.2025.2515655
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