TY  - JOUR
AU  - Alonso de la Vega, Alicia
AU  - Temiz, Nuri Alpay
AU  - Tasakis, Rafail
AU  - Somogyi, Kalman
AU  - Salgueiro, Lorena
AU  - Zimmer, Eleni
AU  - Ramos, Maria
AU  - Diaz-Jimenez, Alberto
AU  - Chocarro, Sara
AU  - Fernández-Vaquero, Mirian
AU  - Stefanovska, Bojana
AU  - Reuveni, Eli
AU  - Ben-David, Uri
AU  - Stenzinger, Albrecht
AU  - Poth, Tanja
AU  - Heikenwälder, Mathias
AU  - Papavasiliou, Nina
AU  - Harris, Reuben S
AU  - Sotillo, Rocio
TI  - Acute expression of human APOBEC3B in mice results in RNA editing and lethality.
JO  - Genome biology
VL  - 24
IS  - 1
SN  - 1465-6906
CY  - London
PB  - BioMed Central
M1  - DKFZ-2023-02493
SP  - 267
PY  - 2023
N1  - #EA:B220#LA:B220#
AB  - 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.
KW  - Humans
KW  - Animals
KW  - Mice
KW  - RNA Editing
KW  - Cytidine Deaminase: genetics
KW  - Cytidine Deaminase: metabolism
KW  - Mutation
KW  - Neoplasms: pathology
KW  - Minor Histocompatibility Antigens: genetics
KW  - Minor Histocompatibility Antigens: metabolism
KW  - DNA: metabolism
KW  - APOBEC3B (Other)
KW  - DNA damage (Other)
KW  - Mouse models (Other)
KW  - Mutations (Other)
KW  - RNA editing (Other)
KW  - Cytidine Deaminase (NLM Chemicals)
KW  - Minor Histocompatibility Antigens (NLM Chemicals)
KW  - DNA (NLM Chemicals)
KW  - APOBEC3B protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:38001542
C2  - pmc:PMC10668425
DO  - DOI:10.1186/s13059-023-03115-4
UR  - https://inrepo02.dkfz.de/record/285670
ER  -