BRG1 and NRG1 form a novel feedback circuit regulating Candida albicans hypha formation and virulence.

BRG1 and NRG1 form a novel feedback circuit regulating Candida albicans hypha formation and virulence.
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DOI:
10.1111/j.1365-2958.2012.08127.x
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发表时间:
2012-08
影响因子:
3.6
通讯作者:
Saville SP
Saville SP
中科院分区:
生物学2区
文献类型:
--
作者:
Cleary IA;Lazzell AL;Monteagudo C;Thomas DP;Saville SP

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在机会性真菌病原体白色念珠菌中,细胞形态和致病能力都受到转录抑制因子Nrg1p的调控。被Nrg1p抑制的基因之一是BRG1,它编码一个可能的GATA家族转录因子。该基因的两个拷贝的缺失阻止了菌丝的形成。我们发现,即使在没有环境刺激的情况下,BRG1的过表达也足以克服Nrg1p介导的抑制,并推动从酵母到菌丝的形态发生转变。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化。对这一现象的分析表明,BRG1的表达是诱导反义NRG1转录所必需的。这是第一次证明了mRNA稳定性在调节白念珠菌毒力的关键特征:形成菌丝的能力方面所起的作用。
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 over-expression 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.
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