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Allosteric Modulation of the Faecalibacterium prausnitzii Hepatitis Delta Virus-like Ribozyme by Glucosamine 6-Phosphate: The Substrate of the Adjacent Gene Product
Biochemistry ( IF 2.9 ) Pub Date : 2017-11-03 00:00:00 , DOI: 10.1021/acs.biochem.7b00879
Luiz F. M. Passalacqua 1 , Randi M. Jimenez 2 , Jennifer Y. Fong 1 , Andrej Lupták 1, 2, 3
Affiliation  

Self-cleaving ribozymes were discovered 30 years ago and have been found throughout nature, from bacteria to animals, but little is known about their biological functions and regulation, particularly how cofactors and metabolites alter their activity. A hepatitis delta virus-like self-cleaving ribozyme maps upstream of a phosphoglucosamine mutase (glmM) open reading frame in the genome of the human gut bacterium Faecalibacterium prausnitzii. The presence of a ribozyme in the untranslated region of glmM suggests a regulation mechanism of gene expression. In the bacterial hexosamine biosynthesis pathway, the enzyme glmM catalyzes the isomerization of glucosamine 6-phosphate into glucosamine 1-phosphate. In this study, we investigated the effect of these metabolites on the co-transcriptional self-cleavage rate of the ribozyme. Our results suggest that glucosamine 6-phosphate, but not glucosamine 1-phosphate, is an allosteric ligand that increases the self-cleavage rate of drz-Fpra-1, providing the first known example of allosteric modulation of a self-cleaving ribozyme by the substrate of the adjacent gene product. Given that the ribozyme is activated by the glmM substrate, but not the product, this allosteric modulation may represent a potential feed-forward mechanism of gene expression regulation in bacteria.

中文翻译:

氨基葡萄糖6-磷酸对Faecalibacterium prausnitzii肝炎三角洲病毒样核酶的变构调节:相邻基因产物的底物

自裂解核酶是在30年前发现的,并已在自然界中发现,从细菌到动物,但对其生物学功能和调节,尤其是辅因子和代谢物如何改变其活性知之甚少。肝炎三角洲病毒样自裂解核酶定位于人类肠道细菌Faecalibacterium prausnitzii基因组中的磷酸葡糖胺变位酶(glmM)开放阅读框的上游glmM非翻译区中存在核酶提示基因表达的调节机制。在细菌己糖胺的生物合成途径中,酶glmM催化6-磷酸氨基葡萄糖异构化为1-磷酸氨基葡萄糖。在这项研究中,我们调查了这些代谢物对核酶共转录自切割率的影响。我们的研究结果表明,氨基葡萄糖6-磷酸而不是氨基葡萄糖1-磷酸是一种变构配体,可提高drz-Fpra-1的自切割率,这提供了第一个已知的自切割核酶变构调节的实例。相邻基因产物的底物。考虑到核酶是由glmM底物激活的,而不是由产物激活的,这种变构调节可能代表了细菌中基因表达调节的潜在前馈机制。
更新日期:2017-11-05
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