ArticleCell death & disease2017
ADAR1-mediated 3' UTR editing and expression control of antiapoptosis genes fine-tunes cellular apoptosis response.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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46 citing papers in PubMed, 63 citations in OpenAlex.
- RNA modifications as determinants of cancer cell death: from epitranscriptomic mechanisms to therapeutic targeting.Functional & integrative genomics · 2026Review
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- ADARs mediate distinct RNA editing activity and gene regulation in theRNA (New York, N.Y.) · 2026Article
- Targeting ADAR1 lactylation activates innate immune and overcomes chemoresistance in ovarian cancer.Cell death and differentiation · 2026Article
- Knockdown of RNA editing proteins reshapes the HepaRG transcriptome and pharmacogene expression.Scientific reports · 2026Article
- ADAR1: a central regulator of dsRNA sensing in host-virus interactions.Frontiers in immunology · 2026Review
- Advances in RNA modification in myocardial fibrosis (Review).International journal of molecular medicine · 2025Review
- ADARs mediate distinct RNA editing activity and gene regulation in thebioRxiv : the preprint server for biology · 2025Article
- Advances in RNA-based cancer therapeutics: pre-clinical and clinical implications.Molecular cancer · 2025Review
- Targeting RNA adenosine editing and modification enzymes for RNA therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- A circularly permuted CasRx platform for efficient, site-specific RNA editing.Nature biotechnology · 2025Article
- Adenosine-to-inosine RNA editing in cancer: molecular mechanisms and downstream targets.Protein & cell · 2025Review
- Article
- Genetic architecture of RNA editing, splicing and gene expression in schizophrenia.Human molecular genetics · 2025Article
- REMR: Identification of RNA Editing-mediated MiRNA Regulation in Cancers.Computational and structural biotechnology journal · 2024Article
- Noncanonical formation of SNX5 gene-derived circular RNA regulates cancer growth.Cell death & disease · 2024Article
- Loss of ADAR1 protein induces changes in small RNA landscape in hepatocytes.RNA (New York, N.Y.) · 2024Article
- A testis-specific lncRNA functions as a post-transcriptional regulator of MDM2 and stimulates apoptosis of testicular germ cell tumor cells.Cell death discovery · 2024Article
- Inverted Alu repeats: friends or foes in the human transcriptome.Experimental & molecular medicine · 2024Review
- The role of ADAR1 through and beyond its editing activity in cancer.Cell communication and signaling : CCS · 2024Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adenosine-to-inosine RNA editing constitutes a crucial component of the cellular transcriptome and critically underpins organism survival and development. While recent high-throughput approaches have provided comprehensive documentation of the RNA editome, its functional output remains mostly unresolved, particularly for events in the non-coding regions. Gene ontology analysis of the known RNA editing targets unveiled a preponderance of genes related to apoptosis regulation, among which proto-oncogenes XIAP and MDM2 encode two the most abundantly edited transcripts. To further decode this potential functional connection, here we showed that the main RNA editor ADAR1 directly targets this 3' UTR editing of XIAP and MDM2, and further exerts a negative regulation on the expression of their protein products. This post-transcriptional silencing role was mediated via the inverted Alu elements in the 3' UTR but independent of alteration in transcript stability or miRNA targeting. Rather, we discovered that ADAR1 competes transcript occupancy with the RNA shuttling factor STAU1 to facilitate nuclear retention of the XIAP and MDM2 mRNAs. As a consequence, ADAR1 may acquire functionality in part by conferring spatial distribution and translation efficiency of the target transcripts. Finally, abrogation of ADAR1 expression or catalytic activity elicited a XIAP-dependent suppression of apoptotic response, whereas ectopic expression reversed this protective effect on cell death. Together, our results extended the known functions of ADAR1 and RNA editing to the critical fine-tuning of the intracellular apoptotic signaling and also provided mechanistic explanation for ADAR1's roles in development and tumorigenesis.
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