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The APOBEC (apolipoprotein B mRNA editing catalytic polypeptide-like) family of proteins have diverse and important functions in human health and disease. These proteins have an intrinsic ability to bind to both RNA and single-stranded (ss) DNA. Both function and tissue-specific expression varies widely for each APOBEC protein. We are beginning to understand that the activity of APOBEC proteins is regulated through genetic alterations, changes in their transcription and mRNA processing, and through their interactions with other macromolecules in the cell. Loss of cellular control of APOBEC activities leads to DNA hypermutation and promiscuous RNA editing associated with the development of cancer or viral drug resistance, underscoring the importance of understanding how APOBEC proteins are regulated.
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http://dx.doi.org/10.1016/j.tibs.2016.05.001 | DOI Listing |
Cell Res
August 2025
State Key Laboratory of Genome and Multi-omics Technologies, Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Gene Editing Technologies (Hainan), Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultu
The vast scope but limited-supporting evidence in sequence databases hinders identification of proteins with specific functionality. Here, we experimentally characterized catalytic efficiency, target site window, motif preference, and off-target activity of 1100 apolipoprotein B mRNA-editing enzyme, catalytic polypeptide (APOBEC)-like family cytidine deaminases (CDs) fused with nCas9 in HEK293T cells, thereby generating the largest dataset of experimentally validated functions for a single protein family to date. These data, together with amino acid sequence, three-dimensional structure, and eight additional features, were used to construct a machine learning (ML) model, AlphaCD, which showed high accuracy in predicting catalytic efficiency (0.
View Article and Find Full Text PDFSci Rep
August 2025
Department of Internal Medicine III With Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center; Paracelsus Medical University, Salzburg Cancer Research Institute - Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Cancer Cluster Salzbu
Cytidine to uridine (C-to-U) as well as adenosine to inosine (A-to-I) RNA editing denotes the posttranscriptional modification of RNA by specialized RNA deaminases. As RNA editing alters the sequence of the RNA, it can affect splicing, stability, miRNA binding and may also lead to recoding of the translated protein. Recently, we analysed recoding A-to-I RNA editing in chronic lymphocytic leukaemia (CLL) and could define prognostically relevant editing patterns.
View Article and Find Full Text PDFMol Ther
August 2025
Department of Cell and Genetic Engineering, BK21 Project, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea; Stem Cell Immunomodulation Research Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. Electronic address: yongsub1.ki
CRISPR-based cytosine base editors enable precise genome editing without inducing double-stranded DNA breaks yet traditionally depend on a limited selection of deaminases from the APOBEC/AID or TadA families. Here, we present SsCBE, a CRISPR-based cytosine base editor utilizing SsdA, a DYW-like deaminase derived from the toxin of Pseudomonas syringae. Strategic engineering of SsdA has led to remarkable improvements in the base editing efficiency (by up to 8.
View Article and Find Full Text PDFSci Rep
July 2025
Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, 40138, Italy.
Recent Monkeypox virus (MPXV) outbreaks in non-endemic regions have highlighted the need for genomic surveillance to support epidemiological investigations and monitor viral evolution. In this paper we present the results of genomic characterization and analyses of mechanisms of human adaptation, including APOBEC-style mutations, performed on 11 MPXV isolates, collected from May to September 2022, from Emilia-Romagna (Italy). Phylogenetic analysis confirmed all strains belonged to Clade IIb.
View Article and Find Full Text PDFLeukemia
September 2025
The Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
ETV6::RUNX1 leukemia is the second most common subtype of childhood B cell acute lymphoblastic leukemia (B-ALL). Although it generally has a low relapse risk, a significant proportion of B-ALL relapses occur within this subtype due to its relatively high incidence. Measurable residual disease at the end of induction therapy is a well-established biomarker predicting treatment outcomes, while no genomic biomarkers are routinely applied in clinics.
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