Editors' ChoiceMicrobiology

Why Pigeon Doo May Be Bad for You

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Science Signaling  16 Nov 2010:
Vol. 3, Issue 148, pp. ec346
DOI: 10.1126/scisignal.3148ec346

In some regions of Africa, a leading cause of death from infection is a yeastlike human pathogen called Cryptococcus neoformans. Its virulence is linked to the mating cycle and production of infectious spores. The organism spends the great majority of its time in the asexual state, but one of the stimuli that can lead to mating is contact with pigeon guano, which leads to increased production of the mating pheromone MFα. The protein Vad1 (for virulence-associated DEAD box protein—D-E-A-D being the single-letter code of Asp-Glu-Ala-Asp) regulates virulence in C. neoformans and has sequence similarity to a family of proteins (those related to RCK/p54, an RNA helicase) that recruit mRNAs to P-bodies, where they are degraded. Park et al. screened C. neoformans for mRNAs that immunoprecipitated with Vad1 to identify its possible targets and found that one of the most highly enriched mRNAs encoded MFα1. Further analysis showed that abundance of MFα1 mRNA increased in cells lacking Vad1 and decreased in cells overexpressing Vad1. Thus, the authors estimated that during the normal asexual cycle, the yeast cells produced 17 times more transcripts for mating pheromone than were actually kept in the cell, only to have them rapidly degraded. Such a “futile cycle” provides a mechanism for rapid response to a stimulus. The authors suspected that, as in muscle metabolism (where futile cycles of phosphorylation and dephosphorylation of fructose 6-phosphate allow small changes in rates of phosphorylation and dephosphorylation to rapidly produce fructose 1,6-bisphosphate for gluconeogenesis during muscle contraction), the futile cycle in yeast mRNA production might allow rapid accumulation of transcripts when conditions favor mating. Indeed, for a nonmotile organism subject to breezes or ripples that can immediately disrupt a mating encounter, prompt response to opportunity may be critical. Consistent with this interpretation, constitutively increased expression of Vad1 in yeast induced to mate by incubation in medium supplemented with pigeon guano still allowed mating, but the process was delayed by about 10 hours.

Y.-D. Park, J. Panepinto, S. Shin, P. Larsen, S. Giles, P. R. Williamson, Mating pheromone in Cryptococcus neoformans is regulated by a transcriptional/degradative “futile” cycle. J. Biol. Chem. 285, 34746–34756 (2010). [Abstract] [Full Text]

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