Eichelman Matthew C, Meyer Michelle M
Department of Biology, Boston College, Chestnut Hill, Massachusetts, USA.
Microbiol Spectr. 2025 Jun 24:e0325224. doi: 10.1128/spectrum.03252-24.
RNA regulators are often found in regulatory networks and mediate growth and virulence in bacteria. Small RNAs (sRNAs) are non-coding RNAs that modulate translation initiation and mRNA degradation by base pairing. To better understand the role of sRNAs in pathogenicity, several studies identified sRNAs in ; however, little functional characterization has followed. This study's goals are to (i) survey putative sRNAs in ; (ii) assess the conservation of these sRNAs; and (iii) examine their predicted targets. Three previous studies in identified 287 putative sRNAs by high-throughput sequencing. This study narrows the candidates down to 58 putative sRNAs. BLAST analysis indicates that the 58 sequences are highly conserved across the pangenome, and 25 are identified sporadically in other Streptococcus species. However, only two have corresponding sequences identified across several Streptococcus species. We used four RNA-target prediction programs to predict targets for each of the 58 putative sRNAs. Across all probable predictions, six sRNAs have overlapping targets predicted by multiple programs, four targeting numerous transposase-encoding transcripts. sRNAs targeting transposase-encoding transcripts display nearly identical and perfect base pairing. One sRNA, M63 (Spd_sr37), has several probable targets in the CcpA regulon, a network responsible for global catabolite repression, suggesting a possible biological function in carbon metabolism control. Each M63-target interaction exhibits unique base pairing, increasing confidence in the biological relevance of the result. This study produces a list of . putative sRNAs whose predicted targets suggest functional significance in transposon and carbon metabolism regulation.
Previous studies identified many small RNA candidates in , several of which were hypothesized to play a role in virulence. Due to the differing sequencing methods, diverse inclusion criteria, strain differences, as well as limited follow-up, it is unclear to what extent candidates identified in different studies have overlapping sequences and functions, and their biological relevance remains ambiguous. This research aims to consolidate the candidate sRNAs across these studies and focuses attention on those that are likely to be regulatory and associated with virulence. This study's findings enhance our knowledge of the conservation of small regulatory RNAs across the many strains and highlight a handful that appear likely to have a role in growth or virulence.
RNA 调控因子常在调控网络中被发现，并介导细菌的生长和毒力。小RNA（sRNA）是非编码RNA，通过碱基配对调节翻译起始和mRNA降解。为了更好地理解sRNA在致病性中的作用，多项研究在[具体细菌名称]中鉴定出了sRNA；然而，后续的功能表征却很少。本研究的目标是：（i）在[具体细菌名称]中调查假定的sRNA；（ii）评估这些sRNA的保守性；（iii）检查它们的预测靶标。之前在[具体细菌名称]中的三项研究通过高通量测序鉴定出了287个假定的sRNA。本研究将候选sRNA数量缩减至58个。BLAST分析表明，这58个序列在[具体细菌名称]的泛基因组中高度保守，其中25个在其他链球菌物种中偶尔被发现。然而，只有两个在多个链球菌物种中鉴定出了相应序列。我们使用四个RNA靶标预测程序来预测这58个假定sRNA各自的靶标。在所有可能的预测中，有六个sRNA有多个程序预测出的重叠靶标，其中四个靶向众多编码转座酶的转录本。靶向编码转座酶转录本的sRNA显示出几乎相同且完美的碱基配对。一个名为M63（Spd_sr37）的sRNA在CcpA调控子中有几个可能的靶标，CcpA调控子是一个负责全局碳代谢物阻遏的网络，这表明它在碳代谢控制中可能具有生物学功能。每个M63与靶标的相互作用都表现出独特的碱基配对，增加了对结果生物学相关性的信心。本研究产生了一份[具体细菌名称]假定sRNA的列表，其预测靶标表明它们在转座子和碳代谢调控中具有功能意义。
之前的研究在[具体细菌名称]中鉴定出了许多小RNA候选物，其中一些被假设在[具体细菌名称]的毒力中发挥作用。由于测序方法不同、纳入标准多样、菌株差异以及后续跟进有限，目前尚不清楚不同研究中鉴定出的候选物在多大程度上具有重叠的序列和功能，其生物学相关性仍不明确。本研究旨在整合这些研究中的候选sRNA，并关注那些可能具有调控作用且与毒力相关的sRNA。本研究的结果增进了我们对众多[具体细菌名称]菌株中小调控RNA保守性的了解，并突出了少数几个似乎可能在生长或毒力中发挥作用的sRNA。
