학술논문
Acute expression of human APOBEC3B in mice results in RNA editing and lethality
Document Type
article
Author
Alicia Alonso de la Vega; Nuri Alpay Temiz; Rafail Tasakis; Kalman Somogyi; Lorena Salgueiro; Eleni Zimmer; Maria Ramos; Alberto Diaz-Jimenez; Sara Chocarro; Mirian Fernández-Vaquero; Bojana Stefanovska; Eli Reuveni; Uri Ben-David; Albrecht Stenzinger; Tanja Poth; Mathias Heikenwälder; Nina Papavasiliou; Reuben S. Harris; Rocio Sotillo
Source
Genome Biology, Vol 24, Iss 1, Pp 1-20 (2023)
Subject
Language
English
ISSN
1474-760X
Abstract
Abstract Background 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. Results 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. Conclusions 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.