APOBEC3B is preferentially expressed at the G2/M phase of cell cycle

• Published in: Biochemical and biophysical research communications 2021-03, Vol.546, p.178-184
• Main Authors: Hirabayashi, Shigeki, Shirakawa, Kotaro, Horisawa, Yoshihito, Matsumoto, Tadahiko, Matsui, Hiroyuki, Yamazaki, Hiroyuki, Sarca, Anamaria Daniela, Kazuma, Yasuhiro, Nomura, Ryosuke, Konishi, Yoshinobu, Takeuchi, Suguru, Stanford, Emani, Kawaji, Hideya, Murakawa, Yasuhiro, Takaori-Kondo, Akifumi
• Format: Article
• Language: English
• Subjects: APOBEC3B; B-Lymphocytes - metabolism; Cell cycle-dependent; Cell Division - genetics; Cells, Cultured; Cytidine Deaminase - genetics; Erythroid Cells - metabolism; G1 Phase - genetics; G2 Phase - genetics; G2/M phase; Humans; Minor Histocompatibility Antigens - genetics; Multiple myeloma; Multiple Myeloma - genetics; Multiple Myeloma - pathology; Neprilysin - metabolism; Normal bone marrow; Plasma Cells - metabolism; RNA, Messenger - analysis; RNA, Messenger - genetics; RNA-Seq; S Phase - genetics; Single-Cell Analysis; Single-cell RNA-Sequencing
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2021.02.008

APOBEC3B (A3B) is a cytosine deaminase that converts cytosine to uracil in single-stranded DNA. Cytosine-to-thymine and cytosine-to-guanine base substitution mutations in trinucleotide motifs (APOBEC mutational signatures) were found in various cancers including lymphoid hematological malignancies such as multiple myeloma and A3B has been shown to be an enzymatic source of mutations in those cancers. Although the importance of A3B is being increasingly recognized, it is unclear how A3B expression is regulated in cancer cells as well as normal cells. To answer these fundamental questions, we analyzed 1276 primary myeloma cells using single-cell RNA-sequencing (scRNA-seq) and found that A3B was preferentially expressed at the G2/M phase, in sharp contrast to the expression patterns of other APOBEC3 genes. Consistently, we demonstrated that A3B protein was preferentially expressed at the G2/M phase in myeloma cells by cell sorting. We also demonstrated that normal blood cells expressing A3B were also enriched in G2/M-phase cells by analyzing scRNA-seq data from 86,493 normal bone marrow mononuclear cells. Furthermore, we revealed that A3B was expressed mainly in plasma cells, CD10+ B cells and erythroid cells, but not in granulocyte-macrophage progenitors. A3B expression profiling in normal blood cells may contribute to understanding the defense mechanism of A3B against viruses, and partially explain the bias of APOBEC mutational signatures in lymphoid but not myeloid malignancies. This study identified the cells and cellular phase in which A3B is highly expressed, which may help reveal the mechanisms behind carcinogenesis and cancer heterogeneity, as well as the biological functions of A3B in normal blood cells. •Single-cell RNA-sequencing revealed preferential expression of A3B at the G2/M phase.•A3B protein expression is higher in G2/M phase than in G1 or S phases in myeloma.•Cell cycle-dependent regulation of A3B is common in myeloma and normal blood cells.•A3B is expressed mainly in plasma cells, CD10+ B cells and erythroid cells.