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

J Mol Biol. 2023 Dec 15;435(24):168333. doi: 10.1016/j.jmb.2023.168333. Epub 2023 Oct 29.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • A1CF protein, human
  • APOBEC-1 Deaminase
  • APOBEC1 protein, human
  • Apolipoproteins B
  • Cytidine
  • RNA, Messenger
  • RNA-Binding Proteins
  • Uridine
  • RBM46 protein, human