Cell-wall synthesis and ribosome maturation are co-regulated by an RNA switch in Mycobacterium tuberculosis.
Cell-wall synthesis and ribosome maturation are co-regulated by an RNA switch in Mycobacterium tuberculosis.
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DOI：
10.1093/nar/gky226
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发表时间：
2018-06-20
影响因子：
14.9
通讯作者：
Arnvig KB
中科院分区：
文献类型：
--
作者：
Schwenk S;Moores A;Nobeli I;McHugh TD;Arnvig KB
结核分枝杆菌的成功依赖于在活跃生长和非复制持久性之间切换的能力，这与潜在的结核病感染有关。复苏促进因子(RPFS)在这些状态之间的转换是必不可少的。RPF的表达受到严格调控，因为这些酶能够降解细胞壁，因此对细菌本身具有潜在的致命性。我们已经在rpfB的5‘非翻译区(UTR)中发现了一个调控元件。我们证明该元件是一个转录调控的RNA开关/核糖开关候选元件，似乎仅限于致病分枝杆菌，暗示了在毒力中的作用。我们使用翻译起始位点映射来重新注释RpfB起始密码子，并鉴定和验证了可能被rpfB反义RNA靶向的核糖体结合位点。最后，我们证明了rpfB与KsgA和ISPE在下游共转录。KsgA编码一种普遍保守的甲基转移酶，参与核糖体成熟，ISPE编码一种参与细胞壁合成的重要激酶。这种安排意味着通过RNA开关对复苏、细胞壁合成和核糖体成熟进行共同调节。
The success of Mycobacterium tuberculosis relies on the ability to switch between active growth and non-replicating persistence, associated with latent TB infection. Resuscitation promoting factors (Rpfs) are essential for the transition between these states. Rpf expression is tightly regulated as these enzymes are able to degrade the cell wall, and hence potentially lethal to the bacterium itself. We have identified a regulatory element in the 5′ untranslated region (UTR) of rpfB. We demonstrate that this element is a transcriptionally regulated RNA switch/riboswitch candidate, which appears to be restricted to pathogenic mycobacteria, suggesting a role in virulence. We have used translation start site mapping to re-annotate the RpfB start codon and identified and validated a ribosome binding site that is likely to be targeted by an rpfB antisense RNA. Finally, we show that rpfB is co-transcribed with ksgA and ispE downstream. ksgA encodes a universally conserved methyltransferase involved in ribosome maturation and ispE encodes an essential kinase involved in cell wall synthesis. This arrangement implies co-regulation of resuscitation, cell wall synthesis and ribosome maturation via the RNA switch.
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影响因子：
3.7
作者：
Moores A;Riesco AB;Schwenk S;Arnvig KB
通讯作者：
Arnvig KB
DOI：
10.1126/science.aad9822
发表时间：
2016-04-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Dar D;Shamir M;Mellin JR;Koutero M;Stern-Ginossar N;Cossart P;Sorek R
通讯作者：
Sorek R
影响因子：
6.4
作者：
Czyz A;Mooney RA;Iaconi A;Landick R
通讯作者：
Landick R
影响因子：
8.8
作者：
Cortes T;Schubert OT;Rose G;Arnvig KB;Comas I;Aebersold R;Young DB
通讯作者：
Young DB
影响因子：
14.9
作者：
Nawrocki EP;Burge SW;Bateman A;Daub J;Eberhardt RY;Eddy SR;Floden EW;Gardner PP;Jones TA;Tate J;Finn RD
通讯作者：
Finn RD