ArticleGenes & development2013
E3-ubiquitin ligase Nedd4 determines the fate of AID-associated RNA polymerase II in B cells.
Article in Genes & development, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- The RNA-Binding Protein PARN Remodeled 3' UTR Structure Defines Poly(A)-Loading Sites to Mediate Immunoglobulin Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Genetic screening identifies Ube2v1 as a suppressor of immunoglobulin class switch recombination in CH12F3 cells.Molecular biology reports · 2025Article
- The USP11/TCEAL1 complex promotes transcription elongation to sustain oncogenic gene expression in neuroblastoma.Genes & development · 2025Article
- The RNA Binding Protein Bcas2 is Required for Antibody Class Switch in Activated-B Cells.Exploration (Beijing, China) · 2025Article
- Transcription elongation factor ELOF1 is required for efficient somatic hypermutation and class switch recombination.Molecular cell · 2025Article
- Activation-induced cytidine deaminase in tertiary lymphoid structures: dual roles and implications in cancer prognosis.Frontiers in oncology · 2025Review
- Transcription elongation factor ELOF1 is required for efficient somatic hypermutation and class switch recombination.bioRxiv : the preprint server for biology · 2024Article
- RNA exosome drives early B cell development via noncoding RNA processing mechanisms.Science immunology · 2022Article
- NEDD4 degrades TUSC2 to promote glioblastoma progression.Cancer letters · 2022Article
- Review
- Regulation of long non-coding RNAs and genome dynamics by the RNA surveillance machinery.Nature reviews. Molecular cell biology · 2020Review
- Molecular regulation of peripheral B cells and their progeny in immunity.Genes & development · 2019Review
- Dismissal of RNA Polymerase II Underlies a Large Ligand-Induced Enhancer Decommissioning Program.Molecular cell · 2018Article
- Human Immunodeficiency Virus Tat Protein Aids V Region Somatic Hypermutation in Human B Cells.mBio · 2018Article
- RNA surveillance by the nuclear RNA exosome: mechanisms and significance.Non-coding RNA · 2018Article
- Lingering Questions about Enhancer RNA and Enhancer Transcription-Coupled Genomic Instability.Trends in genetics : TIG · 2017Review
- Gender Differences in Global but Not Targeted Demethylation in iPSC Reprogramming.Cell reports · 2017Article
- The regulation and functions of the nuclear RNA exosome complex.Nature reviews. Molecular cell biology · 2016Review
- Nbs1 ChIP-Seq Identifies Off-Target DNA Double-Strand Breaks Induced by AID in Activated Splenic B Cells.PLoS genetics · 2015Article
- RNA exosome-regulated long non-coding RNA transcription controls super-enhancer activity.Cell · 2015Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Programmed mutagenesis of the immunoglobulin locus of B lymphocytes during class switch recombination (CSR) and somatic hypermutation requires RNA polymerase II (polII) transcription complex-dependent targeting of the DNA mutator activation-induced cytidine deaminase (AID). AID deaminates cytidine residues on substrate sequences in the immunoglobulin (Ig) locus via a transcription-dependent mechanism, and this activity is stimulated by the RNA polII stalling cofactor Spt5 and the 11-subunit cellular noncoding RNA 3'-5' exonucleolytic processing complex RNA exosome. The mechanism by which the RNA exosome recognizes immunoglobulin locus RNA substrates to stimulate AID DNA deamination activity on its in vivo substrate sequences is an important question. Here we report that E3-ubiquitin ligase Nedd4 destabilizes AID-associated RNA polII by a ubiquitination event, leading to generation of 3' end free RNA exosome RNA substrates at the Ig locus and other AID target sequences genome-wide. We found that lack of Nedd4 activity in B cells leads to accumulation of RNA exosome substrates at AID target genes and defective CSR. Taken together, our study links noncoding RNA processing following RNA polII pausing with regulation of the mutator AID protein. Our study also identifies Nedd4 as a regulator of noncoding RNAs that are generated by stalled RNA polII genome-wide.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.