Antisense and yet sensitive: Copy number control of rolling circle-replicating plasmids by small RNAs

24 p.-6 fig. Dedicated to Prof. Ramón Díaz-Orejas on occasion of his retirement.Bacterial plasmids constitute a wealth of shared DNA amounting to about 20% of the total prokaryotic pangenome. Plasmids replicate autonomously and control their replication by maintaining a fairly constant number of copies within a given host. Plasmids should acquire a good fitness to their hosts so that they do not constitute a genetic load. Here we review some basic concepts in plasmid biology, pertaining to the control of replication and distribution of plasmid copies among daughter cells. A particular class of plasmids is constituted by those that replicate by the rolling circle mode (rolling circle-replicating [RCR]-plasmids). They are small double-stranded DNA molecules, with a rather high number of copies in the original host. RCR-plasmids control their replication by means of a small short-lived antisense RNA, alone or in combination with a plasmid-encoded transcriptional repressor protein. Two plasmid prototypes have been studied in depth, namely the staphylococcal plasmid pT181 and the streptococcal plasmid pMV158, each corresponding to the two types of replication control circuits, respectively. We further discuss possible applications of the plasmid-encoded antisense RNAs and address some future directions that, in our opinion, should be pursued in the study of these small molecules. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems.Peer reviewe