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 (conserved virulence factor D), since loss of the protein results in attenuation of virulence in a murine pneumonia model. We report that deletion of cvfD impacts the expression of 144 transcripts, including the pst1 operon, 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 binding phoU2 mRNA 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.

中文翻译：

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S1域RNA结合蛋白CvfD是一种新型的转录后调节剂，可介导肺炎链球菌D39中的冷敏性，磷酸盐转运和毒力。

转录后基因调控通常涉及RNA结合蛋白，该蛋白直接通过蛋白质-RNA相互作用或通过促进小调控RNA（sRNA）的退火而间接调控mRNA的翻译和/或稳定性。人类病原体肺炎链球菌D39（肺炎球菌）即使含有至少112个sRNA的基因，也不会编码已知与促进sRNA稳定性和功能有关的RNA结合蛋白（例如Hfq或ProQ）的同源物。但是，肺炎球菌基因组包含其他RNA结合蛋白的基因，包括至少六个S1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质。在这里，我们描述这些保守，但是未鉴定，S1结构域蛋白的一个功能，SPD_1366，我们已经改名CvfD（ç onserved v irulence ˚F演员d），因为在小鼠肺炎的致病力的衰减蛋白的丧失导致模型。我们报告说删除cvfD影响144转录本的表达，包括pst1操纵子，编码肺炎链球菌中的磷酸盐转运系统1 。我们进一步表明，CvfD通过结合phoU2在转录后调节肺炎球菌双磷酸盐转运系统的PhoU2主调节剂。mRNA和影响PhoU2的翻译。CvfD不仅控制磷酸盐转运蛋白基因的表达，而且还发挥多效调节剂的作用，影响寒冷敏感性以及涉及多种细胞功能（包括锰吸收和锌外排）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了广泛的影响，部分原因是转录后基因调控。