Following the success of mRNA vaccines against COVID-19, mRNA-based therapeutics have now become a great interest and potential. The development of this approach has been preceded by studies of modifications found on mRNA ribonucleotides that influence the stability, translation and immunogenicity of this molecule. The 5' cap of eukaryotic mRNA plays a critical role in these cellular functions and is thus the focus of intensive chemical modifications to affect the biological properties of in vitro-prepared mRNA. Enzymatic removal of the 5' cap affects the stability of mRNA in vivo. The NUDIX hydrolase Dcp2 was identified as the first eukaryotic decapping enzyme and is routinely used to analyse the synthetic cap at the 5' end of RNA. Here we highlight three additional NUDIX enzymes with known decapping activity, namely Nudt2, Nudt12 and Nudt16. These enzymes possess a different and some overlapping activity towards numerous 5' RNA cap structures, including non-canonical and chemically modified ones. Therefore, they appear as potent tools for comprehensive in vitro characterisation of capped RNA transcripts, with special focus on synthetic RNAs with therapeutic activity.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11434898 | PMC |
| http://dx.doi.org/10.3390/ph17091195 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A fusion protein of polyphosphate kinase 1 (PPK1) and a Nudix hydrolase is involved in inorganic polyphosphate accumulation in the unicellular red alga Cyanidioschyzon merolae.
Plant Mol Biol
December 2024
Department of Gene Function and Phenomics, National Institute of Genetics, Shizuoka, 411-8540, Japan.
Inorganic polyphosphate (polyP) is a linear polymer of phosphate that plays various roles in cells, including in phosphate and metal homeostasis. Homologs of the vacuolar transporter chaperone 4 (VTC4), catalyzing polyP synthesis in many eukaryotes, are absent in red algae, which are among the earliest divergent plant lineages. We identified homologs of polyphosphate kinase 1 (PPK1), a conserved polyP synthase in bacteria, in 42 eukaryotic genomes, including 31 species detected in this study and 12 species of red algae.
View Article and Find Full Text PDFEfficacy and safety of azathioprine in patients with Cronkhite-Canada syndrome: a case series from Peking Union Medical College Hospital.
BMC Pharmacol Toxicol
December 2024
Department of Gastroenterology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China.
Background: Cronkhite-Canada syndrome (CCS) is a rare non-hereditary chronic inflammatory disease characteristic of gastrointestinal polyps and ectodermal abnormalities. Corticosteroid therapy is the mainstay medication for CCS. Few studies indicated immunosuppressants might be the choices for patients with steroid refractory, steroid dependent or intolerant.
View Article and Find Full Text PDFTherapeutic Agents and Patient Characteristics Affecting Metabolism of Thiopurines in Patients with Inflammatory Bowel Disease.
Fukushima J Med Sci
January 2025
Department of Coloproctology and Gastroenterology, Aizu Medical Center Fukushima Medical University.
Objectives: In inflammatory bowel disease therapy, thiopurines have been essential. However, several reports have investigated factors affecting thiopurine metabolism to date. This study investigated factors affecting intracellular concentrations of 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP) in a real-world setting.
View Article and Find Full Text PDFCoupling cellular drug-target engagement to downstream pharmacology with CeTEAM.
Nat Commun
December 2024
Science for Life Laboratory, Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, SE-141 52, Sweden.
Cellular target engagement technologies enable quantification of intracellular drug binding; however, simultaneous assessment of drug-associated phenotypes has proven challenging. Here, we present cellular target engagement by accumulation of mutant as a platform that can concomitantly evaluate drug-target interactions and phenotypic responses using conditionally stabilized drug biosensors. We observe that drug-responsive proteotypes are prevalent among reported mutants of known drug targets.
View Article and Find Full Text PDFTargeting Nudix Hydrolase 5 with Bioactive Flavonoids: Molecular Dynamics and Docking Studies for Breast Cancer Therapy.
Cell Biochem Biophys
December 2024
INTI International University, Nilai, Negeri Sembilan, Malaysia.
Breast cancer (BC) is the most prevalent malignancy among women globally and the leading cause of cancer-related mortality. Consequently, there is an urgent need for new, effective treatment strategies for breast cancer. Research has shown that the enzyme nudix hydrolase 5 (NUDT5) plays a critical role in promoting breast cancer aggressiveness and serves as a key regulator of oncogenic pathways.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!