ArticleNucleic acids research2022
A common transcriptional mechanism involving R-loop and RNA abasic site regulates an enhancer RNA of APOE.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- The role of R-loops-mediated epigenetic regulation in genome stability maintenance and disease pathogenesis: a systematic review.Epigenetics · 2026Pooled it
- Regulation of neuronal transcription by RNA-binding proteins via R-loop dynamics.Neural regeneration research · 2026Article
- Quantum chemical profiling of the electronic structure and hydrolytic stability of modified ribonucleosides.Physical chemistry chemical physics : PCCP · 2026Article
- Review
- N 6 -methyladenosine modification regulates cell death in cognitive impairment.Neural regeneration research · 2026Article
- Harmonized nucleoside mass spectrometry enables reproducible cross-platform RNA modification quantification.bioRxiv : the preprint server for biology · 2026Article
- When R-Loops Go Awry: Genome Instability and Neurological Diseases.The European journal of neuroscience · 2026Review
- Resolution of R-loops and transcription-replication conflicts by SETX-BRCA1-BARD1 complex.Nature structural & molecular biology · 2026Article
- Emerging roles of circular RNAs and enhancer RNAs: new insights into the development and management of neurodegenerative disorders.Biomarker research · 2026Review
- Deciphering the regulatory landscape of enhancer RNAs in health and disease.Signal transduction and targeted therapy · 2026Review
- Lysosomal proteomics reveals mechanisms of neuronal APOE4-associated lysosomal dysfunction.Autophagy · 2025Article
- Lysosomal proteomics reveals mechanisms of neuronal apoE4-associated lysosomal dysfunction.bioRxiv : the preprint server for biology · 2025Article
- RNA damage and its implications in genome stability.DNA repair · 2025Review
- An Update on Neuroaging on Earth and in Spaceflight.International journal of molecular sciences · 2025Review
- A model for a dual function of NNature genetics · 2024Article
- The enhancer RNA, AANCR, regulates APOE expression in astrocytes and microglia.Nucleic acids research · 2024Article
- Article
- Intertwining roles of R-loops and G-quadruplexes in DNA repair, transcription and genome organization.Nature cell biology · 2024Review
- An Emerging Role for Enhancer RNAs in Brain Disorders.Neuromolecular medicine · 2024Review
- Cell type-specific roles of APOE4 in Alzheimer disease.Nature reviews. Neuroscience · 2024Review
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
RNA is modified by hundreds of chemical reactions and folds into innumerable shapes. However, the regulatory role of RNA sequence and structure and how dysregulation leads to diseases remain largely unknown. Here, we uncovered a mechanism where RNA abasic sites in R-loops regulate transcription by pausing RNA polymerase II. We found an enhancer RNA, AANCR, that regulates the transcription and expression of apolipoprotein E (APOE). In some human cells such as fibroblasts, AANCR is folded into an R-loop and modified by N-glycosidic cleavage; in this form, AANCR is a partially transcribed nonfunctional enhancer and APOE is not expressed. In contrast, in other cell types including hepatocytes and under stress, AANCR does not form a stable R-loop as its sequence is not modified, so it is transcribed into a full-length enhancer that promotes APOE expression. DNA sequence variants in AANCR are associated significantly with APOE expression and Alzheimer's Disease, thus AANCR is a modifier of Alzheimer's Disease. Besides AANCR, thousands of noncoding RNAs are regulated by abasic sites in R-loops. Together our data reveal the essentiality of the folding and modification of RNA in cellular regulation and demonstrate that dysregulation underlies common complex diseases such as Alzheimer's disease.
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