RrmA regulates the stability of specific transcripts in response to both nitrogen source and oxidative stress.

RrmA regulates the stability of specific transcripts in response to both nitrogen source and oxidative stress.
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DOI:
10.1111/mmi.12324
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发表时间:
2013-09
影响因子:
3.6
通讯作者:
Caddick MX
Caddick MX
中科院分区:
生物学2区
文献类型:
--
作者:
Krol K;Morozov IY;Jones MG;Wyszomirski T;Weglenski P;Dzikowska A;Caddick MX

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转录物稳定性的差异调节是生物体调节基因表达的有效手段。一个充分表征的例子是谷氨酰胺在构巢曲霉中特异性转录物的信号降解。在编码介导氮代谢物阻遏的宽域转录因子areA的情况下,信号通过3′ UTR的高度保守区域介导。利用该RNA序列,我们分离出RrmA,一种RNA识别基序蛋白。相应基因的破坏导致谷氨酰胺信号的转录物降解以及硝酸盐信号的niaD mRNA的稳定性的损失。然而,氮饥饿被证明在稳定某些转录物中独立于RrmA起作用。RrmA还参与精氨酸催化酶基因表达的调节和mRNA稳定性水平的氧化应激反应。ΔrrmA突变体对氧化应激高度敏感。这种表型与eifE和dhsA mRNA的不稳定相关。eifE编码eIF5A,eIF5A是一种翻译因子,其中保守的赖氨酸在翻译后被修饰为羟腐胺赖氨酸,这是一个需要DhsA的过程。有趣的是,对于特定的转录物,RrmA介导稳定化和不稳定化,并且转导的信号的特异性是转录物依赖性的,这表明它与转录物之间不同的其他因子协同作用。
Differential regulation of transcript stability is an effective means by which an organism can modulate gene expression. A well-characterized example is glutamine signalled degradation of specific transcripts in Aspergillus nidulans. In the case of areA, which encodes a wide-domain transcription factor mediating nitrogen metabolite repression, the signal is mediated through a highly conserved region of the 3′ UTR. Utilizing this RNA sequence we isolated RrmA, an RNA recognition motif protein. Disruption of the respective gene led to loss of both glutamine signalled transcript degradation as well as nitrate signalled stabilization of niaD mRNA. However, nitrogen starvation was shown to act independently of RrmA in stabilizing certain transcripts. RrmA was also implicated in the regulation of arginine catabolism gene expression and the oxidative stress responses at the level of mRNA stability. ΔrrmA mutants are hypersensitive to oxidative stress. This phenotype correlates with destabilization of eifE and dhsA mRNA. eifE encodes eIF5A, a translation factor within which a conserved lysine is post-translationally modified to hypusine, a process requiring DhsA. Intriguingly, for specific transcripts RrmA mediates both stabilization and destabilization and the specificity of the signals transduced is transcript dependent, suggesting it acts in consort with other factors which differ between transcripts.
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