Acute expression of human APOBEC3B in mice results in RNA editing and lethality

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

doi:10.1186/s13059-023-03115-4

Acute expression of human APOBEC3B in mice results in RNA editing and lethality

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

Human Molecular Genetics Biochemistry

Tel Aviv University

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	267
Journal	GENOME BIOLOGY
Volume	24
Issue number	1
DOIs	https://doi.org/10.1186/s13059-023-03115-4
State	Published - 24 Nov 2023

Keywords

APOBEC3B
DNA damage
Mouse models
Mutations
RNA editing

All Science Journal Classification (ASJC) codes

Ecology, Evolution, Behavior and Systematics
Genetics
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s13059-023-03115-4

Cite this

Alonso de la Vega, A., Temiz, N. A., Tasakis, R., Somogyi, K., Salgueiro, L., Zimmer, E., Ramos, M., Diaz-Jimenez, A., Chocarro, S., Fernández-Vaquero, M., Stefanovska, B., Reuveni, E., Ben-David, U., Stenzinger, A., Poth, T., Heikenwälder, M., Papavasiliou, N., Harris, R. S., & Sotillo, R. (2023). Acute expression of human APOBEC3B in mice results in RNA editing and lethality. GENOME BIOLOGY, 24(1), Article 267. https://doi.org/10.1186/s13059-023-03115-4

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title = "Acute expression of human APOBEC3B in mice results in RNA editing and lethality",

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.",

keywords = "APOBEC3B, DNA damage, Mouse models, Mutations, RNA editing",

author = "{Alonso de la Vega}, Alicia and Temiz, {Nuri Alpay} and Rafail Tasakis and Kalman Somogyi and Lorena Salgueiro and Eleni Zimmer and Maria Ramos and Alberto Diaz-Jimenez and Sara Chocarro and Mirian Fern{\'a}ndez-Vaquero and Bojana Stefanovska and Eli Reuveni and Uri Ben-David and Albrecht Stenzinger and Tanja Poth and Mathias Heikenw{\"a}lder and Nina Papavasiliou and Harris, {Reuben S.} and Rocio Sotillo",

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month = nov,

day = "24",

doi = "10.1186/s13059-023-03115-4",

language = "الإنجليزيّة",

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Alonso de la Vega, A, Temiz, NA, Tasakis, R, Somogyi, K, Salgueiro, L, Zimmer, E, Ramos, M, Diaz-Jimenez, A, Chocarro, S, Fernández-Vaquero, M, Stefanovska, B, Reuveni, E, Ben-David, U, Stenzinger, A, Poth, T, Heikenwälder, M, Papavasiliou, N, Harris, RS & Sotillo, R 2023, 'Acute expression of human APOBEC3B in mice results in RNA editing and lethality', GENOME BIOLOGY, vol. 24, no. 1, 267. https://doi.org/10.1186/s13059-023-03115-4

TY - JOUR

T1 - Acute expression of human APOBEC3B in mice results in RNA editing and lethality

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

PY - 2023/11/24

Y1 - 2023/11/24

N2 - 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.

AB - 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.

KW - APOBEC3B

KW - DNA damage

KW - Mouse models

KW - Mutations

KW - RNA editing

UR - http://www.scopus.com/inward/record.url?scp=85177771194&partnerID=8YFLogxK

U2 - 10.1186/s13059-023-03115-4

DO - 10.1186/s13059-023-03115-4

M3 - مقالة

C2 - 38001542

SN - 1474-7596

VL - 24

JO - GENOME BIOLOGY

JF - GENOME BIOLOGY

IS - 1

M1 - 267

ER -

Acute expression of human APOBEC3B in mice results in RNA editing and lethality

Abstract

Keywords

All Science Journal Classification (ASJC) codes

UN SDGs

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