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J. Biol. Chem. 285 (45): 34746-34756

© 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

Mating Pheromone in Cryptococcus neoformans Is Regulated by a Transcriptional/Degradative "Futile" Cycle*Formula

Yoon-Dong Park{ddagger}, John Panepinto§, Soowan Shin, Peter Larsen||, Steven Giles**, , and Peter R. Williamson{ddagger}1

From the {ddagger}Laboratory of Clinical Infectious Diseases, NIAID, National Institutes of Health, Bethesda, Maryland 20892,
the §Department of Microbiology and Immunology, Witebsky Center for Microbial Pathogenesis and Immunology, University of Buffalo, Buffalo, New York 14214,
the Section of Infectious Diseases, Department of Medicine, University of Illinois, Chicago, Illinois 60612,
the ||Biosciences Division, Argonne National Laboratory, Lemont, Illinois 60439, and
the **Department of Bacteriology, University of Wisconsin, Madison, Wisconsin 53701

ABSTRACT Back to Top

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 ~17-fold excess of MF{alpha} 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 MF{alpha} 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 MF{alpha} 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 MF{alpha} transcripts in a synthetic/degradative cycle, providing a mechanism of mRNA induction for time-critical cellular events, such as mating induction.

Key Words: Cell Differentiation • Eukaryote • Gene Expression • RNA-binding Protein • RNA Synthesis • Yeast • Cryptococcus neoformans • RNA Stability • Mating Pheromone

Received for publication April 21, 2010. Revision received August 12, 2010.

1 To whom correspondence should be addressed: 9000 Rockville Pike, Bldg. 10, Rm. 11N234, MSC 1888, Bethesda, MD 20892. Fax: 301-480-7321; E-mail: williamsonpr{at}

A Novel Specificity Protein 1 (SP1)-like Gene Regulating Protein Kinase C-1 (Pkc1)-dependent Cell Wall Integrity and Virulence Factors in Cryptococcus neoformans.
A. Adler, Y.-D. Park, P. Larsen, V. Nagarajan, K. Wollenberg, J. Qiu, T. G. Myers, and P. R. Williamson (2011)
J. Biol. Chem. 286, 20977-20990
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