Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
The enzymes catalysing the modification of the wobble uridine (U) of tRNAs (U-enzymes) play an important role in tumor development. We have recently demonstrated that the U-enzymes are crucial in the survival of glycolytic melanoma cultures through a codon-specific regulation of HIF1α mRNA translation. Moreover, depletion of U-enzymes resensitizes resistant melanoma to targeted therapy. These results indicate that targeting U-enzymes represents a new therapeutic opportunity for melanoma patients.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276846 | PMC |
| http://dx.doi.org/10.1080/23723556.2018.1513725 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Metastasis is the leading cause of cancer related deaths, however therapies specifically targeting metastasis are lacking and remain a dire therapeutic need in the clinic. Metastasis is a highly inefficient process that is inhibited by extracellular stress. Therefore, metastasizing cells that ultimately survive and successfully colonize distant organs must undergo molecular rewiring to mitigate stress.
View Article and Find Full Text PDFCryo-EM structures of the MnmE-MnmG complex reveal large conformational changes and provide new insights into the mechanism of tRNA modification.
Nucleic Acids Res
August 2025
Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, Brussels 1050, Belgium.
MnmE and MnmG form a conserved protein complex responsible for the addition of a 5-carboxymethylaminomethyl (cmnm5) group onto the wobble uridine of several transfer RNAs (tRNAs). Within this complex, both proteins collaborate intensively to catalyze a tRNA modification reaction that involves glycine as a substrate in addition to three different cofactors, with FAD and NADH binding to MnmG and methylenetetrahydrofolate (5,10-CH2-THF) to MnmE. Without structures of the MnmEG complex, it remained enigmatic how these substrates and co-factors can be brought together in a concerted manner.
View Article and Find Full Text PDF8-Oxo-7,8-dihydropurines as Building Blocks to Enhance the Selectivity of an RNA Aptamer for Aminoglycosides.
ACS Chem Biol
August 2025
Department of Chemistry, University of Colorado Denver, Science Building 1151 Arapahoe Street, Denver, Colorado 80204, United States.
The use of nucleic acids as potential therapeutic tools, sensors, or biomaterials, among other applications, has dramatically increased. Among these, RNA aptamers are of interest due to an innate high specificity toward their cognate targets, which include small molecules, proteins, ions, or cells. In this work, we took advantage of the ability that 8-oxo-7,8-dihydroguanine (8-oxoG) has to participate in unique H-bonding interactions, and probed its use to increase/control the selectivity/affinity of aptamers of RNA and DNA.
View Article and Find Full Text PDFUridines Modified with Sulfur or Selenium in U-G Wobble Pairs Matter for tRNA Function.
Curr Med Chem
August 2025
Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Department of Bioorganic Chemistry, Sienkiewicza 112, 90-363, Lodz, Poland.
Transfer RNAs (tRNAs) are ubiquitous in cells and are essential for the translation of genetic information from messenger RNA (mRNA) into proteins in all three domains of life. They act as adaptors that decode mRNA codons via their anticodons and deliver the corresponding amino acids to the growing polypeptide chain. Currently, over 100 modified nucleosides have been found in tRNA that are crucial for the integrity and functionality of this molecule.
View Article and Find Full Text PDFAn Oxyprenylated Phenylpropanoid Pharmacologic Scaffold for SelU Inhibition.
Chembiochem
August 2025
Department of Chemistry and University at Albany, State University of New York, 1400 Washington Ave., Albany, NY, 12222, USA.
MnmH, better known as tRNA 2-selenouridine synthase (SelU), is a member of the Mnm family enzymes that work in concert to modify uridine at the wobble position. Instrumental in maintaining base pair fidelity and exclusive to bacteria, SelU is a promising drug target. Although no molecular structure has been experimentally calculated, insights into this enzyme's mechanism of catalysis have been empirically gleaned and proven useful for ligand-based rational drug design.
View Article and Find Full Text PDF