Regulation of Neisseria meningitidis cytochrome bc₁ components by NrrF, a Fur‐controlled small noncoding RNA

Abstract

NrrF is a small regulatory RNA of the human pathogen Neisseria meningitidis . NrrF was previously shown to repress succinate dehydrogenase ( sdh CDAB ) under control of the ferric uptake regulator (Fur). Here, we provide evidence that cytochrome bc 1 , encoded by the polycistronic mRNA pet ABC , is a NrrF target as well. We demonstrated differential expression of cytochrome bc 1 comparing wild‐type meningococci and meningococci expressing NrrF when sufficient iron is available. Using a gfp ‐reporter system monitoring translational control and target recognition of sRNA in Escherichia coli , we show that interaction between NrrF and the 5′ untranslated region of the pet ABC mRNA results in its repression. The NrrF region essential for repression of pet ABC was identified by site‐directed mutagenesis and is fully conserved among meningococci. Our results provide further insights into the mechanism by which Fur controls essential components of the N. meningitidis respiratory chain. Adaptation of cytochrome bc 1 complex component levels upon iron limitation is post‐transcriptionally regulated via the small regulatory RNA NrrF.

sRNA EsrE Is Transcriptionally Regulated by the Ferric Uptake Regulator Fur in Escherichia coli

“…For instance, Fur represses the expression of RyhB sRNA, which downregulates at least six mRNAs encoding iron-binding proteins, including sdhCDAB operon encoding succinate dehydrogenase in E. coli [ 44 ]. Moreover, sdhCDAB is regulated by NrrF sRNA as well, the expression of which is controlled by Fur in the human pathogen Neisseria meningitidis [ 45 ]. Thus, this phenomenon is common in the regulatory network of bacteria, showing that bacteria can regulate the expression of genes in cells layer by layer, and control their metabolism reasonably and effectively.…”

Impacts of Small RNAs and Their Chaperones on Bacterial Pathogenicity

“…Numerous additional orthologs of RyhB have now been identified in both Gram-positive and Gram-negative bacterial species, with varying dependencies on Hfq. Like PrrF, these orthologs share little to no sequence similarities to RyhB (or PrrF), but they exert similar effects on gene expression and iron homeostasis (Mellin et al, 2007;Ducey et al, 2009;Metruccio et al, 2009;Jackson et al, 2013;Santana et al, 2014;Pannekoek et al, 2017;Sass and Coenye, 2020). However, the specific impacts of iron-responsive sRNAs and Hfq on virulence of these organisms has yet to be fully elucidated.…”