The posttranscriptional recoding of nuclear RNA transcripts has emerged as an important regulatory mechanism during eukaryotic gene expression. In particular the deamination of adenosine to inosine (interpreted by the translational machinery as a guanosine) is a frequent event that can recode the meaning of amino acid codons in translated exons, lead to structural changes in the RNA fold, or may affect splice consensus or regulatory sequence sites in noncoding exons or introns and modulate the biogenesis of small RNAs. The molecular mechanism of how the RNA editing machinery and its substrates recognize and interact with each other is not understood well enough to allow for the ab initio delineation of bona fide RNA editing sites. However, progress in the identification of various physiological modification sites and their characterization has given important insights regarding molecular features and events critical for productive RNA editing reactions. In addition, structural studies using components of the RNA editing machinery and together with editing competent substrate molecules have provided information on the chemical mechanism of adenosine deamination within the context of RNA molecules. Here, I give an overview of the process of adenosine deamination RNA editing and describe its relationship to other RNA processing events and its currently established roles in gene regulation.
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http://dx.doi.org/10.1016/B978-0-12-386497-0.00006-2 | DOI Listing |
Cancer Chemother Pharmacol
January 2025
Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China.
Purpose: Ovarian clear cell carcinoma is a highly malignant gynecological tumor characterized by a high rate of chemotherapy resistance and poor prognosis. The PI3K/AKT/mTOR pathway is well-known to be closely related to the progression of various malignancies, and recent studies have indicated that this pathway may play a critical role in the progression and worsening of OCCC.
Methods: In this study, we investigated the combined effects of WX390, a dual inhibitor of PI3K/mTOR, and cisplatin on OCCC through both in vitro and in vivo experiments to further elucidate their therapeutic effects.
EMBO Rep
January 2025
Myeloid Therapeutics Inc., Cambridge, MA, 02139, USA.
To address a wide range of genetic diseases, genome editing tools that can achieve targeted delivery of large genes without causing double-strand breaks (DSBs) or requiring DNA templates are necessary. Here, we introduce CRISPR-Enabled Autonomous Transposable Element (CREATE), a genome editing system that combines the programmability and precision of CRISPR/Cas9 with the RNA-mediated gene insertion capabilities of the human LINE-1 (L1) element. CREATE employs a modified L1 mRNA to carry a payload gene, and a Cas9 nickase to facilitate targeted editing by L1-mediated reverse transcription and integration without relying on DSBs or DNA templates.
View Article and Find Full Text PDFSci Rep
January 2025
Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
Antibody-drug conjugates (ADCs) are an emerging strategy in cancer therapy, enhancing precision and efficacy by linking targeted antibodies to potent cytotoxic agents. This study introduces a novel ADC that combines ribonuclease A (RNase A) with cetuximab (Cet), an anti-EGFR monoclonal antibody, through a polyethylene glycol (PEG) linker (RN-PEG-Cet), aimed to induce apoptosis in KRAS mutant colorectal cancer (CRC) via a ROS-mediated pathway. RN-PEG-Cet was successfully synthesized and characterized for its physicochemical properties, retaining full enzymatic activity in RNA degradation and high binding affinity to EGFR.
View Article and Find Full Text PDFACS Synth Biol
January 2025
Laboratory of Synthetic Microbiology, School of Chemical Engineering & Technology, Tianjin University, Tianjin 300072, P. R. China.
The fusion expression of deoxyribonucleic acid (DNA) replication-related proteins with nucleotide deaminase enzymes promotes random mutations in bacterial genomes, thereby increasing genetic diversity among the population. Most previous studies have focused on cytosine deaminase, which produces only C → T mutations, significantly limiting the variety of mutation types. In this study, we developed a fusion expression system by combining DnaG (RNA primase) with adenine deaminase TadA-8e (DnaG-TadA) in , which is capable of rapidly introducing A → G mutations into the genome, resulting in a 664-fold increase in terms of mutation rate.
View Article and Find Full Text PDFCurr Opin Microbiol
January 2025
Gulbenkian Institute for Molecular Medicine (GIMM), Avenida Professor Egas Moniz, Lisboa, Portugal. Electronic address:
Genome editing technologies, such as CRISPR-Cas9, have revolutionised the study of genes in a variety of organisms, including unicellular parasites. Today, the CRISPR-Cas9 technology is vastly applied in high-throughput screens to investigate interactions between the Apicomplexan parasite Toxoplasma gondii and its hosts. In vitro and in vivo T.
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