Unité des Interactions Bactéries-Cellules, Institut Pasteur, Paris, France ; INSERM, U604, Paris, France ; INRA, USC2020, Paris, France.
Unité de Génomique Evolutive des Microbes, Institut Pasteur, Paris, France ; CNRS, UMR3525, Paris, France.
PLoS Genet. 2014 Jan;10(1):e1004065. doi: 10.1371/journal.pgen.1004065. Epub 2014 Jan 9.
The human bacterial pathogen Listeria monocytogenes is emerging as a model organism to study RNA-mediated regulation in pathogenic bacteria. A class of non-coding RNAs called CRISPRs (clustered regularly interspaced short palindromic repeats) has been described to confer bacterial resistance against invading bacteriophages and conjugative plasmids. CRISPR function relies on the activity of CRISPR associated (cas) genes that encode a large family of proteins with nuclease or helicase activities and DNA and RNA binding domains. Here, we characterized a CRISPR element (RliB) that is expressed and processed in the L. monocytogenes strain EGD-e, which is completely devoid of cas genes. Structural probing revealed that RliB has an unexpected secondary structure comprising basepair interactions between the repeats and the adjacent spacers in place of canonical hairpins formed by the palindromic repeats. Moreover, in contrast to other CRISPR-Cas systems identified in Listeria, RliB-CRISPR is ubiquitously present among Listeria genomes at the same genomic locus and is never associated with the cas genes. We showed that RliB-CRISPR is a substrate for the endogenously encoded polynucleotide phosphorylase (PNPase) enzyme. The spacers of the different Listeria RliB-CRISPRs share many sequences with temperate and virulent phages. Furthermore, we show that a cas-less RliB-CRISPR lowers the acquisition frequency of a plasmid carrying the matching protospacer, provided that trans encoded cas genes of a second CRISPR-Cas system are present in the genome. Importantly, we show that PNPase is required for RliB-CRISPR mediated DNA interference. Altogether, our data reveal a yet undescribed CRISPR system whose both processing and activity depend on PNPase, highlighting a new and unexpected function for PNPase in "CRISPRology".
人类细菌病原体李斯特菌正在成为研究 RNA 介导的致病性细菌调控的模式生物。一类被称为 CRISPRs(成簇的、规律间隔的短回文重复序列)的非编码 RNA 已被描述为赋予细菌抵抗入侵噬菌体和可转移质粒的能力。CRISPR 的功能依赖于 CRISPR 相关(cas)基因的活性,这些基因编码一大类具有核酸酶或解旋酶活性以及 DNA 和 RNA 结合结构域的蛋白质。在这里,我们对 L. monocytogenes 菌株 EGD-e 中表达和加工的 CRISPR 元件(RliB)进行了表征,该菌株完全缺乏 cas 基因。结构探测表明,RliB 具有意想不到的二级结构,其中重复序列和相邻间隔区之间存在碱基对相互作用,而不是由回文重复序列形成的典型发夹结构。此外,与李斯特菌中鉴定的其他 CRISPR-Cas 系统不同,RliB-CRISPR 在李斯特菌基因组中普遍存在于相同的基因组位置,并且从不与 cas 基因相关。我们表明,RliB-CRISPR 是内源性编码多核苷酸磷酸化酶(PNPase)酶的底物。不同李斯特菌 RliB-CRISPR 的间隔区与温和和毒性噬菌体有许多共同序列。此外,我们表明,cas 缺失的 RliB-CRISPR 降低了携带匹配原间隔区的质粒的获取频率,前提是基因组中存在第二个 CRISPR-Cas 系统的转录 cas 基因。重要的是,我们表明 PNPase 是 RliB-CRISPR 介导的 DNA 干扰所必需的。总之,我们的数据揭示了一个尚未描述的 CRISPR 系统,其加工和活性都依赖于 PNPase,突出了 PNPase 在“CRISPRology”中的一个新的、意想不到的功能。