Pichon Christophe, Felden Brice
Biochimie Pharmaceutique, Université de Rennes I, Unité Propre de Recherche de l'Enseignement Supérieur JE 2311, Inserm ESPRI, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France.
Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14249-54. doi: 10.1073/pnas.0503838102. Epub 2005 Sep 23.
Small RNA (sRNA) genes are expressed in all organisms, primarily as regulators of translation and message stability. We have developed comparative genomic approaches to identify sRNAs that are expressed by Staphylococcus aureus, the most common cause of hospital-acquired infections. This study represents an in-depth analysis of the RNome of a Gram-positive bacterium. A set of sRNAs candidates were identified in silico within intergenic regions, and their expression levels were monitored by using microarrays and confirmed by Northern blot hybridizations. Two sRNAs were also detected directly from purification and RNA sequence determination. In total, at least 12 sRNAs are expressed from the S. aureus genome, five from the core genome and seven from pathogenicity islands that confer virulence and antibiotic resistance. Three sRNAs are present in multiple (two to five) copies. For the sRNAs that are conserved throughout the bacterial phylogeny, their secondary structures were inferred by phylogenetic comparative methods. In vitro binding assays indicate that one sRNA encoded within a pathogenicity island is a trans-encoded antisense RNA regulating the expression of target genes at the posttranscriptional level. Some of these RNAs show large variations of expression among pathogenic strains, suggesting that they are involved in the regulation of staphylococcal virulence.
小RNA(sRNA)基因在所有生物体中均有表达,主要作为翻译和信息稳定性的调节因子。我们已经开发出比较基因组学方法来鉴定由金黄色葡萄球菌表达的sRNA,金黄色葡萄球菌是医院获得性感染最常见的病因。这项研究代表了对革兰氏阳性细菌RNA组的深入分析。在基因间区域通过计算机分析鉴定出一组sRNA候选物,并使用微阵列监测它们的表达水平,并用Northern印迹杂交进行确认。还通过纯化和RNA序列测定直接检测到两种sRNA。金黄色葡萄球菌基因组总共至少表达12种sRNA,其中5种来自核心基因组,7种来自赋予毒力和抗生素抗性的致病岛。三种sRNA以多个(两到五个)拷贝存在。对于在整个细菌系统发育中保守的sRNA,通过系统发育比较方法推断其二级结构。体外结合试验表明,致病岛内编码的一种sRNA是一种反式编码的反义RNA,在转录后水平调节靶基因的表达。其中一些RNA在致病菌株之间表现出很大的表达差异,表明它们参与了葡萄球菌毒力的调节。