Journal Article

DKFZ-2023-02493

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Acute expression of human APOBEC3B in mice results in RNA editing and lethality.

Alonso de la Vega, A. (First author)DKFZ* ; Temiz, N. A. ; Tasakis, R.DKFZ* ; Somogyi, K.DKFZ* ; Salgueiro, L.DKFZ* ; Zimmer, E.DKFZ* ; Ramos, M.DKFZ* ; Diaz-Jimenez, A.DKFZ* ; Chocarro, S.DKFZ* ; Fernández-Vaquero, M.DKFZ* ; Stefanovska, B. ; Reuveni, E. ; Ben-David, U. ; Stenzinger, A. ; Poth, T. ; Heikenwälder, M.DKFZ* ; Papavasiliou, N.DKFZ* ; Harris, R. S. ; Sotillo, R. (Last author)DKFZ*

2023
BioMed Central London

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Please use a persistent id in citations: doi:10.1186/s13059-023-03115-4

Abstract: 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.

Keyword(s): Humans (MeSH) ; Animals (MeSH) ; Mice (MeSH) ; RNA Editing (MeSH) ; Cytidine Deaminase: genetics (MeSH) ; Cytidine Deaminase: metabolism (MeSH) ; Mutation (MeSH) ; Neoplasms: pathology (MeSH) ; Minor Histocompatibility Antigens: genetics (MeSH) ; Minor Histocompatibility Antigens: metabolism (MeSH) ; DNA: metabolism (MeSH) ; APOBEC3B ; DNA damage ; Mouse models ; Mutations ; RNA editing ; Cytidine Deaminase ; Minor Histocompatibility Antigens ; DNA ; APOBEC3B protein, human

Note: #EA:B220#LA:B220#

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Contributing Institute(s):

1. B220 Molekulare Grundlagen thorakaler Tumoren (B220)
2. F180 Chronische Entzündung und Krebs (F180)
3. D150 Immundiversität (D150)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2023

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