While virulence properties of Candida albicans, the most commonly isolated human fungal pathogen, are controlled by transcriptional and post-translational mechanisms, considerably little is known about the role of post-transcriptional, and particularly translational, mechanisms. We demonstrate that UME6, a key filament-specific transcriptional regulator whose expression level is sufficient to determine C. albicans morphology and promote virulence, has one of the longest 5' untranslated regions (UTRs) identified in fungi to date, which is predicted to form a complex and extremely stable secondary structure. The 5' UTR inhibits the ability of UME6, when expressed at constitutive high levels, to drive complete hyphal growth, but does not cause a reduction in UME6 transcript. Deletion of the 5' UTR increases C. albicans filamentation under a variety of conditions but does not affect UME6 transcript level or induction kinetics. We show that the 5' UTR functions to inhibit Ume6 protein expression under several filament-inducing conditions and specifically reduces association of the UME6 transcript with polysomes. Overall, our findings suggest that translational efficiency mechanisms, known to regulate diverse biological processes in bacterial and viral pathogens as well as higher eukaryotes, have evolved to inhibit and fine-tune morphogenesis, a key virulence trait of many human fungal pathogens.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032089 | PMC |
http://dx.doi.org/10.1111/mmi.12576 | DOI Listing |
mSphere
December 2024
Department of Microbiology, University of Georgia, Athens, Georgia, USA.
Unlabelled: Prominent virulence traits of include its ability to produce filamentous hyphal cells and grow as a biofilm. These traits are under control of numerous transcription factors (TFs), including Brg1 and Rme1. In the reference strain SC5314, a Δ/Δ mutant has reduced levels of biofilm/filament production; a Δ/Δ Δ/Δ double mutant has wild-type levels of biofilm/filament production.
View Article and Find Full Text PDFACS Synth Biol
December 2024
Structural Biology Initiative, CUNY Advanced Science Research Center, New York, New York 10031, United States.
Microbiol Spectr
November 2024
Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
is a yeast pathogen causing nosocomial outbreaks of candidemia. Its ability to adhere to inert surfaces and to be transmitted from one patient to another via medical devices is of particular concern. Like other spp.
View Article and Find Full Text PDFbioRxiv
October 2024
Structural Biology Initiative, CUNY Advanced Science Research Center, New York, NY 10031.
Blue light illumination can be detected by Light-Oxygen-Voltage (LOV) photosensing proteins and translated into a range of biochemical responses, facilitating the generation of novel optogenetic tools to control cellular function. Here, we develop new variants of our previously described VP-EL222 light-dependent transcription factor and apply them to study the phosphate-responsive signaling () pathway in the budding yeast , exemplifying the utilities of these new tools. Focusing first on the VP-EL222 protein itself, we quantified the tunability of gene expression as a function of light intensity and duration, and demonstrated that this system can tolerate the addition of substantially larger effector domains without impacting function.
View Article and Find Full Text PDFEMBO J
August 2024
The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
Starvation in diploid budding yeast cells triggers a cell-fate program culminating in meiosis and spore formation. Transcriptional activation of early meiotic genes (EMGs) hinges on the master regulator Ime1, its DNA-binding partner Ume6, and GSK-3β kinase Rim11. Phosphorylation of Ume6 by Rim11 is required for EMG activation.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!