Identification of RBM46 as a novel APOBEC1 cofactor for C-to-U RNA-editing activity

• Published in: Journal of molecular biology Vol. 435; no. 24; p. 168333
• Main Authors: Wang, Shanshan, Kim, Kyumin, Gelvez, Nicolas, Chung, Claire, Gout, Jean-Francois, Fixman, Benjamin, Vermulst, Marc, Chen, Xiaojiang S
• Format: Journal Article
• Language: English
• Published: Netherlands 15.12.2023
• Subjects: APOBEC-1 Deaminase - genetics; APOBEC-1 Deaminase - metabolism; Apolipoproteins B - genetics; Apolipoproteins B - metabolism; Cytidine - genetics; Cytidine - metabolism; HEK293 Cells; Humans; RNA Editing; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Uridine - genetics; Uridine - metabolism
• ISSN: 0022-2836; 1089-8638; 1089-8638
• DOI: 10.1016/j.jmb.2023.168333

Cytidine (C) to Uridine (U) RNA editing is a post-transcription modification that is involved in diverse biological processes. APOBEC1 (A1) catalyzes the conversion of C-to-U in RNA, which is important in regulating cholesterol metabolism through its editing activity on ApoB mRNA. However, A1 requires a cofactor to form an "editosome" for RNA editing activity. A1CF and RBM47, both RNA-binding proteins, have been identified as cofactors that pair with A1 to form editosomes and edit ApoB mRNA and other cellular RNAs. SYNCRIP is another RNA-binding protein that has been reported as a potential regulator of A1, although it is not directly involved in A1 RNA editing activity. Here, we describe the identification and characterization of a novel cofactor, RBM46 (RNA-Binding-Motif-protein-46), that can facilitate A1 to perform C-to-U editing on ApoB mRNA. Additionally, using the low-error circular RNA sequencing technique, we identified novel cellular RNA targets for the A1/RBM46 editosome. Our findings provide further insight into the complex regulatory network of RNA editing and the potential new function of A1 with its cofactors.