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ADAR Therapeutics as a New Tool for Personalized Medicine.
Genes (Basel)
January 2025
Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
In the field of RNA therapy, innovative approaches based on adenosine deaminases acting on RNA (ADAR)-mediated site-directed RNA editing (SDRE) have been established, providing an exciting opportunity for RNA therapeutics. ADAR1 and ADAR2 enzymes are accountable for the predominant form of RNA editing in humans, which involves the hydrolytic deamination of adenosine (A) to inosine (I). This inosine is subsequently interpreted as guanosine (G) by the translational and splicing machinery because of their structural similarity.
View Article and Find Full Text PDFFusion circRNA F-circEA1 facilitates EML4-ALK1 positive lung adenocarcinoma progression through the miR-4673/SMAD4/ADAR1 axis.
Cell Signal
December 2024
Department of Respiratory Medicine, Jinling Hospital, Nanjing Medical University, Jiangsu Province, China. Electronic address:
Circular RNA (circRNA) can sponge miRNA participate in the tumorigenesis and progression of various cancers. We substantiate for the first time that the fusion circular RNA (F-circRNA) F-circEA1 is involved in driving the echinoderm microtubule associated-protein like 4-anaplastic lymphoma kinase variant 1-positive (EML4-ALK1) lung adenocarcinoma (LUAD) progression and the expression of the parental gene EML4-ALK1, molecular mechanisms of F-circEA1 in the EML4-ALK1 LUAD remain unknown. Bioinformatics analysis showed that only miR-4673 can bind to F-circEA1 and bind to EML4-ALK1 3'-UTR to regulate the expression of EML4-ALK1.
View Article and Find Full Text PDFDistinct interactomes of ADAR1 nuclear and cytoplasmic protein isoforms and their responses to interferon induction.
Nucleic Acids Res
December 2024
Central European Institute of Technology (CEITEC), Masaryk University, Kamenice 5, Brno 62500, Czechia.
The RNA editing enzyme adenosine deaminase acting on RNA 1 (ADAR1) is essential for correct functioning of innate immune responses. The ADAR1p110 isoform is mainly nuclear and ADAR1p150, which is interferon (IFN) inducible, is predominately cytoplasmic. Using three different methods - co-immunoprecipitation (co-IP) of endogenous ADAR1, Strep-tag co-IP and BioID with individual ADAR1 isoforms - a comprehensive interactome was generated during both homeostasis and the IFN response.
View Article and Find Full Text PDFImmunomodulatory agents (IMiDs) are a major class of drugs for treating multiple myeloma (MM); however, acquired resistance to IMiDs remains a significant clinical challenge. While alterations in cereblon (CRBN) and its pathway are known to contribute to IMiD resistance, they account for only 20-30% of cases, and the underlying mechanisms in the majority of the resistance cases remain unclear. Here, we identified ADAR1 as a novel driver of lenalidomide resistance in MM.
View Article and Find Full Text PDFADAR1 expression in different cancer cell lines and its change under heat shock.
J Appl Genet
December 2024
Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Święcickiego 6 Street, 60-781, Poznań, Poland.
Adenosine deaminase acting on RNA 1 (ADAR1) plays an essential role in the development of malignancies by modifying the expression of different oncogenes. ADAR1 presents three distinct activities: adenosine-to-inosine RNA editing, modulating IFN pathways, and response to cellular stress factors. Following stressors such as heat shock, ADAR1p110 isoform relocates from the nucleus to the cytoplasm, where it suppresses RNA degradation which leads to the arrest of apoptosis and cell survival.
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