Exploring the regulatory potential of RNA structures in 202 cyanobacterial genomes.

Cyanobacteria are one of the oldest and most abundant groups of prokaryotes and are crucial for research in climate, ecology, medicine, and agriculture. Despite intensive efforts in metabolic engineering of cyanobacteria, the mechanisms of gene regulation, particularly through regulatory RNA structures, are often ignored. We computationally searched 202 cyanobacterial genomes for putative conserved RNA structures (CRSs) in the upstream and downstream intergenic regions of 931 orthologous gene groups with the comparative genomics tool CMfinder. The predicted structures were scored according to their local phylogeny and filtered for a maximal false discovery rate of 10%. The screen identified 402 CRSs that match known RNA families (Rfam and Rho-independent bacterial terminators) and 409 novel CRSs. The structures are not limited to either low or high nucleotide conservation, and about half have a high level of significant covariation. The majority of novel CRSs are supported by transcription in at least one species in public RNA-seq data. The regulatory associations of CRSs are discussed in different metabolic pathways, such as photosynthesis, nitrogen fixation, and CO$_2$ metabolism. This resource will support future research on the regulatory mechanisms of RNA in cyanobacteria.