Protein interaction map of APOBEC3 enzyme family reveals deamination-independent role in cellular function

• DOI: 10.1101/2024.02.06.579137
• Publication Date: 2024-02-07T04:55:17Z
• Authors: Gwendolyn M. Jang; Arun Kumar Annan ...; Arzhang Shayeganmehr; Erika Prando Munhoz; Reanna Lao; Amit Gaba; Milaid Granadillo...; Robin P. Love; Benjamin J. Polacco; Yuan Zhou; Nevan J. Krogan; Robyn M. Kaake; Linda Chelico
• Keywords: Deamination

Human APOBEC3 enzymes are a family of single-stranded (ss)DNA and RNA cytidine deaminases that act as part the intrinsic immunity against viruses retroelements. These deaminate cytosine to form uracil which can functionally inactivate or cause degradation viral retroelement genomes. In addition, APOBEC3s have deamination independent antiviral activity through protein nucleic acid interactions. If expression levels misregulated, some access human genome leading mutagenesis, contributing cancer initiation evolution. While known interact with large ribonucleoprotein complexes, function dependence is not entirely understood. To further understand their cellular roles, we determined by affinity purification mass spectrometry (AP-MS) interaction network for map diverse set protein-protein protein-RNA mediated Our analysis identified novel RNA-mediated interactions between APOBEC3C, APOBEC3H Haplotype I II, APOBEC3G spliceosome proteins, proteins involved in tRNA methylation ncRNA export from nucleus. RNA-independent APOBEC3B, APOBEC3D, APOBEC3F prefoldin folding chaperones. Interaction 5 (PFD5) APOBEC3B disrupted ability PFD5 induce oncogene cMyc, implicating cancer. Altogether, results uncover functions suggest they may fundamental roles biology, redundant, there tumor suppressors, suggesting role biology.