Laboratoire de Chimie des Processus Biologiques, CNRS-UMR 8229, Collège De France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France.
Published: February 2018
AI Article Synopsis
Article Abstract
Post-transcriptional base modifications are important to the maturation process of transfer RNAs (tRNAs). Certain modifications are abundant and present at several positions in tRNA as for example the dihydrouridine, a modified base found in the three domains of life. Even though the function of dihydrourine is not well understood, its high content in tRNAs from psychrophilic bacteria or cancer cells obviously emphasizes a central role in cell adaptation. The reduction of uridine to dihydrouridine is catalyzed by a large family of flavoenzymes named dihydrouridine synthases (Dus). Prokaryotes have three Dus (A, B and C) wherein DusB is considered as an ancestral protein from which the two others derived via gene duplications. Here, we unequivocally established the complete substrate specificities of the three Escherichia coli Dus and solved the crystal structure of DusB, enabling for the first time an exhaustive structural comparison between these bacterial flavoenzymes. Based on our results, we propose an evolutionary scenario explaining how substrate specificities has been diversified from a single structural fold.
The study investigates how dihydrouridine modifications in tRNA affect gene expression during stress, particularly in response to oxidative conditions in Escherichia coli.
Researchers manipulated the redox state using paraquat and found that different tRNA-dihydrouridine synthases (DusA, DusB, DusC) have varying sensitivities to oxidative stress, influencing dihydrouridine levels.
The findings highlight the role of NADPH availability in tRNA modification and provide new insights into how cells respond to oxidative stress through redox dynamics.
Department of Thoracic Surgery, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Gansu Province Key Laboratory of Environmental Oncology, Lanzhou 730030, China. Electronic address:
Objective: Limited research has focused on the role of dihydrouridine synthases (DUS) family members in human tumors. Our previous findings indicated an impact of dihydrouridine synthase 4 like (DUS4L) on cell proliferation and apoptosis in lung adenocarcinoma (LUAD) A549 cell, yet its broader functions and regulatory mechanisms in LUAD remain elusive.
Methods: Using a LUAD tissue microarray and immunohistochemical (IHC) staining, we validated variations in DUS4L protein expression levels among LUAD patients and assessed its clinical significance.
Sorbonne Université, CNRS, Institut de Biologie Paris Seine, Biology of Aging and Adaptation, Institut de Biologie Paris-Seine, F-75252 Paris Cedex 05, France.
Dihydrouridine (D), a prevalent and evolutionarily conserved base in the transcriptome, primarily resides in tRNAs and, to a lesser extent, in mRNAs. Notably, this modification is found at position 2449 in the 23S rRNA, strategically positioned near the ribosome's peptidyl transferase site. Despite the prior identification, in genome, of three dihydrouridine synthases (DUS), a set of NADPH and FMN-dependent enzymes known for introducing D in tRNAs and mRNAs, characterization of the enzyme responsible for D2449 deposition has remained elusive.
Introduction: is a popular edible fungus with high economic and nutritional value. However, the rot disease caused by , pose a serious threat to the quality and yield of . Biological control is one of the effective ways to control fungal diseases.
The post-transcriptional reduction of uridine to dihydrouridine (D) by dihydrouridine synthase (DUS) enzymes is among the most ubiquitous transformations in RNA biology. D is found at multiple sites in tRNAs, and studies in yeast have proposed that each of the four eukaryotic DUS enzymes modifies a different site; however, the molecular basis for this exquisite selectivity is unknown, and human DUS enzymes have remained largely uncharacterized. Here we investigate the substrate specificity of human dihydrouridine synthase 2 (hDUS2) using mechanism-based cross-linking with 5-bromouridine (5-BrUrd)-modified oligonucleotide probes and dihydrouridylation assays.
