Gene miaA for post-transcriptional modification of tRNAXXA is important for morphological and metabolic differentiation in Streptomyces
Gene miaA for post-transcriptional modification of tRNAXXA is important for morphological and metabolic differentiation in Streptomyces
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DOI：
10.1111/mmi.14266
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发表时间：
2019-07-01
影响因子：
3.6
通讯作者：
Ostash, Bohdan
中科院分区：
文献类型：
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作者：
Koshla, Oksana;Yushchuk, Oleksandr;Ostash, Bohdan
放线菌属链霉菌的成员具有复杂的生命周期，是生物活性次级代谢产物的最深来源。虽然形态发生和次生代谢受转录共调控，链霉菌采用额外的机制来启动上述过程。这种机制是基于唯一的同源tRNA（UAA）（Leu）（由bldA编码）延迟翻译稀有亮氨酰密码子UUA。基于bldA的遗传开关是链霉菌中翻译调控的广泛记录的例子。然而，在bldA发现50年后，塑造其功能和特殊条件的因素仍然难以捉摸。在这里，我们解决的假设，转录后tRNA修饰发挥作用的tRNA为基础的翻译控制链霉菌的机制。特别地，我们研究了白色链霉菌J1074的两个基因XNR_1074（miaA）和XNR_1078（miaB），它们分别编码tRNA（腺苷（37）-N6）-二甲基烯丙基转移酶和tRNA（N6-异戊烯基腺苷（37）-C2）-甲硫基转移酶。这些酶以顺序的方式在大多数含A36-A37的tRNA中产生高度修饰的ms（2）i（6）A37残基。我们发现S. miaB，尤其是miaA无效突变体。具有改变的形态发生和次生代谢。我们提供的遗传学证据表明，miaA缺陷影响基因表达的翻译水平，最有可能是通过密码子UXX和UUA的解码受损。
Members of actinobacterial genus Streptomyces possess a sophisticated life cycle and are the deepest source of bioactive secondary metabolites. Although morphogenesis and secondary metabolism are subject to transcriptional co-regulation, streptomycetes employ an additional mechanism to initiate the aforementioned processes. This mechanism is based on delayed translation of rare leucyl codon UUA by the only cognate tRNA(UAA)(Leu) (encoded by bldA). The bldA-based genetic switch is an extensively documented example of translational regulation in Streptomyces. Yet, after five decades since the discovery of bldA, factors that shape its function and peculiar conditionality remained elusive. Here we address the hypothesis that post-transcriptional tRNA modifications play a role in tRNA-based mechanisms of translational control in Streptomyces. Particularly, we studied two Streptomyces albus J1074 genes, XNR_1074 (miaA) and XNR_1078 (miaB), encoding tRNA (adenosine(37)-N6)-dimethylallyltransferase and tRNA (N6-isopentenyl adenosine(37)-C2)-methylthiotransferase respectively. These enzymes produce, in a sequential manner, a hypermodified ms(2)i(6)A37 residue in most of the A36-A37-containing tRNAs. We show that miaB and especially miaA null mutant of S. albus possess altered morphogenesis and secondary metabolism. We provide genetic evidence that miaA deficiency impacts translational level of gene expression, most likely through impaired decoding of codons UXX and UUA in particular.