S1 Domain RNA-Binding Protein CvfD Is a New Posttranscriptional Regulator That Mediates Cold Sensitivity, Phosphate Transport, and Virulence in Streptococcus pneumoniae D39.
S1 Domain RNA-Binding Protein CvfD Is a New Posttranscriptional Regulator That Mediates Cold Sensitivity, Phosphate Transport, and Virulence in Streptococcus pneumoniae D39.
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S1 结构域 RNA 结合蛋白 CvfD 是一种新型转录后调节因子，可介导肺炎链球菌 D39 的冷敏感性、磷酸盐转运和毒力。
DOI：
10.1128/jb.00245-20
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发表时间：
2020
影响因子：
3.2
通讯作者：
Winkler,MalcolmE
中科院分区：
文献类型：
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作者：
Sinha,Dhriti;Zheng,JiaqiJ;Tsui,Ho-ChingTiffany;Richardson,JohnD;DeLay,NicholasR;Winkler,MalcolmE
转录后基因调控通常涉及RNA结合蛋白，其直接通过蛋白质-RNA相互作用或间接通过促进小调节RNA（sRNA）的退火来调节mRNA翻译和/或稳定性。人类病原体肺炎链球菌D39（肺炎球菌）不编码已知参与促进sRNA稳定性和功能的RNA结合蛋白（如Hfq或ProQ）的同源物，尽管它含有至少112种sRNA的基因。然而，肺炎球菌基因组中含有其他RNA结合蛋白的基因，包括至少六种S1结构域蛋白：核糖体蛋白S1（rpsA）、多核苷酸磷酸化酶（pnpA）、RNase R（rnr）和三种功能未知的蛋白。在这里，我们的特点之一，这些保守的，但未表征，S1结构域蛋白，SPD_1366，我们已更名为CvfD（conservedefficiencefactorD）的功能，因为蛋白质的损失导致在小鼠肺炎模型中的毒力减弱。我们报道了cvfD的缺失影响了144个转录本的表达，包括编码磷酸盐转运系统1的pst 1操纵子。肺炎。我们进一步表明，CvfD转录后调节肺炎球菌双磷酸转运系统的主调节因子PhoU 2通过bindingphoU 2 mRNA和影响PhoU 2翻译。CvfD不仅控制磷酸盐转运蛋白基因的表达，而且还作为多效性调节剂发挥作用，其影响冷敏感性以及参与多种细胞功能（包括锰吸收和锌流出）的sRNA和基因的表达。总之，我们的数据表明，CvfD对肺炎球菌的生理和毒力产生广泛的影响，部分是通过转录后基因调控。肺炎。然而，对肺炎球菌中参与RNA生物学的大多数sRNA或RNA结合蛋白的功能知之甚少。在本文中，我们表征的表型和一个目标的S1结构域RNA结合蛋白CvfD，一个同源物的一般应力蛋白13确定，但没有广泛的特点，在其他Firmicutesspecies。肺炎球菌CvfD是一种广泛的多效性调节因子，其缺乏导致二价阳离子稳态的失调、磷酸盐摄取的PhoU 2主调节因子的翻译减少、代谢和sRNA量改变、冷敏感性和毒力减弱。这些发现强调了RNA生物学在肺炎球菌生理学和毒力中的关键作用。
Posttranscriptional gene regulation often involves RNA-binding proteins that modulate mRNA translation and/or stability either directly through protein-RNA interactions or indirectly by facilitating the annealing of small regulatory RNAs (sRNAs). The human pathogen Streptococcus pneumoniae D39 (pneumococcus) does not encode homologs to RNA-binding proteins known to be involved in promoting sRNA stability and function, such as Hfq or ProQ, even though it contains genes for at least 112 sRNAs. However, the pneumococcal genome contains genes for other RNA-binding proteins, including at least six S1 domain proteins: ribosomal protein S1 (rpsA), polynucleotide phosphorylase (pnpA), RNase R (rnr), and three proteins with unknown functions. Here, we characterize the function of one of these conserved, yet uncharacterized, S1 domain proteins, SPD_1366, which we have renamed CvfD (conservedvirulencefactorD), since loss of the protein results in attenuation of virulence in a murine pneumonia model. We report that deletion ofcvfDimpacts the expression of 144 transcripts, including thepst1operon, encoding phosphate transport system 1 in S. pneumoniae. We further show that CvfD posttranscriptionally regulates the PhoU2 master regulator of the pneumococcal dual-phosphate transport system by bindingphoU2mRNA and impacting PhoU2 translation. CvfD not only controls expression of phosphate transporter genes but also functions as a pleiotropic regulator that impacts cold sensitivity and the expression of sRNAs and genes involved in diverse cellular functions, including manganese uptake and zinc efflux. Together, our data show that CvfD exerts a broad impact on pneumococcal physiology and virulence, partly by posttranscriptional gene regulation.IMPORTANCERecent advances have led to the identification of numerous sRNAs in the major human respiratory pathogen S. pneumoniae. However, little is known about the functions of most sRNAs or RNA-binding proteins involved in RNA biology in pneumococcus. In this paper, we characterize the phenotypes and one target of the S1 domain RNA-binding protein CvfD, a homolog of general stress protein 13 identified, but not extensively characterized, in otherFirmicutesspecies. Pneumococcal CvfD is a broadly pleiotropic regulator, whose absence results in misregulation of divalent cation homeostasis, reduced translation of the PhoU2 master regulator of phosphate uptake, altered metabolism and sRNA amounts, cold sensitivity, and attenuation of virulence. These findings underscore the critical roles of RNA biology in pneumococcal physiology and virulence.