| Title: | Mating pheromone in Cryptococcus neoformans is regulated by a transcriptional/degradative 'futile' cycle |
| Author(s): | Park YD; Panepinto J; Shin S; Larsen P; Giles S; Williamson PR; |
| Address: | "Laboratory of Clinical Infectious Diseases, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA" |
| ISSN/ISBN: | 1083-351X (Electronic) 0021-9258 (Print) 0021-9258 (Linking) |
| Abstract: | "Sexual reproduction in fungi requires induction of signaling pheromones within environments that are conducive to mating. The fungus Cryptococcus neoformans is currently the fourth greatest cause of infectious death in regions of Africa and undergoes mating in phytonutrient-rich environments to create spores with infectious potential. Here we show that under conditions where sexual development is inhibited, a approximately 17-fold excess of MFalpha pheromone transcript is synthesized and then degraded by a DEAD box protein, Vad1, resulting in low steady state transcript levels. Transfer to mating medium or deletion of the VAD1 gene resulted in high level accumulation of MFalpha transcripts and enhanced mating, acting in concert with the mating-related HOG1 pathway. We then investigated whether the high metabolic cost of this apparently futile transcriptional cycle could be justified by a more rapid induction of mating. Maintenance of Vad1 activity on inductive mating medium by constitutive expression resulted in repressed levels of MFalpha that did not prevent but rather prolonged the time to successful mating from 5-6 h to 15 h (p < 0.0001). In sum, these data suggest that VAD1 negatively regulates the sexual cell cycle via degradation of constitutive high levels of MFalpha transcripts in a synthetic/degradative cycle, providing a mechanism of mRNA induction for time-critical cellular events, such as mating induction" |
| Keywords: | "Africa/epidemiology Cell Cycle/*physiology Cryptococcosis/epidemiology/genetics/metabolism Cryptococcus neoformans/pathogenicity/*physiology Fungal Proteins/*biosynthesis/genetics Humans Pheromones/*biosynthesis/genetics Spores, Fungal/genetics/*metabolis;" |
| Notes: | "MedlinePark, Yoon-Dong Panepinto, John Shin, Soowan Larsen, Peter Giles, Steven Williamson, Peter R eng AI45995/AI/NIAID NIH HHS/ R01 AI049371/AI/NIAID NIH HHS/ R01 AI045995/AI/NIAID NIH HHS/ ImNIH/Intramural NIH HHS/ AI49371/AI/NIAID NIH HHS/ Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't 2010/08/31 J Biol Chem. 2010 Nov 5; 285(45):34746-56. doi: 10.1074/jbc.M110.136812. Epub 2010 Aug 27" |
