Department of Biology, The University of Texas at San Antonio, San Antonio, TX 78249, USA.
Mol Microbiol. 2012 Aug;85(3):557-73. doi: 10.1111/j.1365-2958.2012.08127.x. Epub 2012 Jul 5.
In the opportunistic fungal pathogen Candida albicans both cellular morphology and the capacity to cause disease are regulated by the transcriptional repressor Nrg1p. One of the genes repressed by Nrg1p is BRG1, which encodes a putative GATA family transcription factor. Deletion of both copies of this gene prevents hypha formation. We discovered that BRG1 overexpression is sufficient to overcome Nrg1p-mediated repression and drive the morphogenetic shift from yeast to hyphae even in the absence of environmental stimuli. We further observed that expression of BRG1 influences the stability of the NRG1 transcript, thus controlling filamentation through a feedback loop. Analysis of this phenomenon revealed that BRG1 expression is required for the induction of an antisense NRG1 transcript. This is the first demonstration of a role for mRNA stability in regulating the key C. albicans virulence trait: the ability to form hyphae.
在机会致病真菌白色念珠菌中，细胞形态和致病能力都受到转录抑制剂 Nrg1p 的调控。Nrg1p 抑制的基因之一是 BRG1，它编码一个假定的 GATA 家族转录因子。该基因的两个拷贝缺失会阻止菌丝形成。我们发现，BRG1 的过表达足以克服 Nrg1p 介导的抑制作用，并驱动从酵母到菌丝的形态发生转变，即使在没有环境刺激的情况下也是如此。我们进一步观察到，BRG1 的表达影响 NRG1 转录本的稳定性，从而通过反馈环控制丝状生长。对这一现象的分析表明，BRG1 的表达是诱导反义 NRG1 转录本所必需的。这是第一个证明 mRNA 稳定性在调节白色念珠菌关键毒力特征：形成菌丝的能力中的作用的例证。
