Small regulatory RNAs (sRNAs) contribute significantly to the post-transcriptional control of gene expression in bacteria. sRNAs may influence mRNA translation and stability by engaging in direct base-pairing interactions with target transcripts. In some cases, a given bacterium expresses multiple, seemingly homologous sRNAs which are called sibling sRNAs. The physiological advantage of encoding several copies of nearly identical regulators or how their activity is integrated into established regulatory circuits is generally not well understood.

The α-proteobacterium Caulobacter crescentus encodes four sibling sRNAs of the αR8 RNA family sharing conserved sequence elements and a characteristic secondary structure. The αR8 sRNAs are expressed from independent genomic loci under different environmental conditions, including carbon availability and iron deficiency, indicating sibling-specific transcriptional input. To determine the target spectra of each family member we performed comparative transcriptome analyses and identified both shared as well as individual target interactions. Additionally, by performing RIL-seq (RNA interaction by ligation and sequencing) we recovered interactions between the the αR8 sRNAs and the sRNA CrfA. CrfA is induced in response to carbon starvation and acts as a sponge RNA that binds to and facilitates the turn-over of its paralogous interaction partners. Using both in vivo as well as in vitro approaches, we have untangled a complex post-transcriptional network modulating carbon metabolism during adaptation to changes in nutrient availability.