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024 7 _ |a 10.1186/s13059-023-03115-4
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024 7 _ |a 1465-6906
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024 7 _ |a 1465-6914
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024 7 _ |a 1474-7596
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100 1 _ |a Alonso de la Vega, Alicia
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245 _ _ |a Acute expression of human APOBEC3B in mice results in RNA editing and lethality.
260 _ _ |a London
|c 2023
|b BioMed Central
336 7 _ |a article
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520 _ _ |a RNA editing has been described as promoting genetic heterogeneity, leading to the development of multiple disorders, including cancer. The cytosine deaminase APOBEC3B is implicated in tumor evolution through DNA mutation, but whether it also functions as an RNA editing enzyme has not been studied.Here, we engineer a novel doxycycline-inducible mouse model of human APOBEC3B-overexpression to understand the impact of this enzyme in tissue homeostasis and address a potential role in C-to-U RNA editing. Elevated and sustained levels of APOBEC3B lead to rapid alteration of cellular fitness, major organ dysfunction, and ultimately lethality in mice. Importantly, RNA-sequencing of mouse tissues expressing high levels of APOBEC3B identifies frequent UCC-to-UUC RNA editing events that are not evident in the corresponding genomic DNA.This work identifies, for the first time, a new deaminase-dependent function for APOBEC3B in RNA editing and presents a preclinical tool to help understand the emerging role of APOBEC3B as a driver of carcinogenesis.
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650 _ 7 |a APOBEC3B
|2 Other
650 _ 7 |a DNA damage
|2 Other
650 _ 7 |a Mouse models
|2 Other
650 _ 7 |a Mutations
|2 Other
650 _ 7 |a RNA editing
|2 Other
650 _ 7 |a Cytidine Deaminase
|0 EC 3.5.4.5
|2 NLM Chemicals
650 _ 7 |a Minor Histocompatibility Antigens
|2 NLM Chemicals
650 _ 7 |a DNA
|0 9007-49-2
|2 NLM Chemicals
650 _ 7 |a APOBEC3B protein, human
|0 EC 3.5.4.5
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a RNA Editing
|2 MeSH
650 _ 2 |a Cytidine Deaminase: genetics
|2 MeSH
650 _ 2 |a Cytidine Deaminase: metabolism
|2 MeSH
650 _ 2 |a Mutation
|2 MeSH
650 _ 2 |a Neoplasms: pathology
|2 MeSH
650 _ 2 |a Minor Histocompatibility Antigens: genetics
|2 MeSH
650 _ 2 |a Minor Histocompatibility Antigens: metabolism
|2 MeSH
650 _ 2 |a DNA: metabolism
|2 MeSH
700 1 _ |a Temiz, Nuri Alpay
|b 1
700 1 _ |a Tasakis, Rafail
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700 1 _ |a Somogyi, Kalman
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700 1 _ |a Salgueiro, Lorena
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700 1 _ |a Zimmer, Eleni
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700 1 _ |a Ramos, Maria
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700 1 _ |a Diaz-Jimenez, Alberto
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700 1 _ |a Chocarro, Sara
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700 1 _ |a Fernández-Vaquero, Mirian
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700 1 _ |a Stefanovska, Bojana
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700 1 _ |a Reuveni, Eli
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700 1 _ |a Ben-David, Uri
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700 1 _ |a Stenzinger, Albrecht
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700 1 _ |a Poth, Tanja
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700 1 _ |a Heikenwälder, Mathias
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700 1 _ |a Papavasiliou, Nina
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700 1 _ |a Harris, Reuben S
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700 1 _ |a Sotillo, Rocio
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773 _ _ |a 10.1186/s13059-023-03115-4
|g Vol. 24, no. 1, p. 267
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