DNA and RNA binding proteins (DRBPs) are a broad class of molecules that regulate numerous cellular processes across all living organisms, creating intricate dynamic multilevel networks to control nucleotide metabolism and gene expression. These interactions are highly regulated, and dysregulation contributes to the development of a variety of diseases, including cancer. An increasing number of proteins with DNA and/or RNA binding activities have been identified in recent years, and it is important to understand how their activities are related to the molecular mechanisms of cancer. In addition, many of these proteins have overlapping functions, and it is therefore essential to analyze not only the loss of function of individual factors, but also to group abnormalities into specific types of activities in regard to particular cancer types. In this review, we summarize the classes of DNA-binding, RNA-binding, and DRBPs, drawing particular attention to the similarities and differences between these protein classes. We also perform a cross-search analysis of relevant protein databases, together with our own pipeline, to identify DRBPs involved in cancer. We discuss the most common DRBPs and how they are related to specific cancers, reviewing their biochemical, molecular biological, and cellular properties to highlight their functions and potential as targets for treatment.
- Klíčová slova
- DNA/RNA binding protein, biomarkers, cancer, mutation, targeted treatment,
- MeSH
- DNA vazebné proteiny metabolismus MeSH
- DNA MeSH
- lidé MeSH
- nádory * genetika metabolismus MeSH
- proteiny vázající RNA * metabolismus MeSH
- RNA genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- DNA vazebné proteiny MeSH
- DNA MeSH
- proteiny vázající RNA * MeSH
- RNA MeSH
Protein-RNA interactions (PRIs) control pivotal steps in RNA biogenesis, regulate multiple physiological and pathological cellular networks, and are emerging as important drug targets. However, targeting of specific protein-RNA interactions for therapeutic developments is still poorly advanced. Studies and manipulation of these interactions are technically challenging and in vitro drug screening assays are often hampered due to the complexity of RNA structures. The binding of nucleolin (NCL) to a G-quadruplex (G4) structure in the messenger RNA (mRNA) of the Epstein-Barr virus (EBV)-encoded EBNA1 has emerged as an interesting therapeutic target to interfere with immune evasion of EBV-associated cancers. Using the NCL-EBNA1 mRNA interaction as a model, we describe a quantitative proximity ligation assay (PLA)-based in cellulo approach to determine the structure activity relationship of small chemical G4 ligands. Our results show how different G4 ligands have different effects on NCL binding to G4 of the EBNA1 mRNA and highlight the importance of in-cellulo screening assays for targeting RNA structure-dependent interactions.
- Klíčová slova
- EBNA1, Epstein-Barr virus (EBV), G-quadruplexes, PhenDC3, protein-mRNA interactions, pyridostatin, structure-activity relationship,
- MeSH
- aminochinoliny chemie MeSH
- biotest metody MeSH
- fosfoproteiny metabolismus MeSH
- G-kvadruplexy * MeSH
- kyseliny pikolinové chemie MeSH
- lidé MeSH
- messenger RNA metabolismus MeSH
- nádorové buněčné linie MeSH
- nukleolin MeSH
- proteiny vázající RNA metabolismus MeSH
- virus Epsteinův-Barrové - jaderné antigeny genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- aminochinoliny MeSH
- EBV-encoded nuclear antigen 1 MeSH Prohlížeč
- fosfoproteiny MeSH
- kyseliny pikolinové MeSH
- messenger RNA MeSH
- proteiny vázající RNA MeSH
- pyridostatin MeSH Prohlížeč
- virus Epsteinův-Barrové - jaderné antigeny MeSH