Abstract
In eukaryotes, RNA species originating from pervasive transcription are regulators of various cellular processes, from the expression of individual genes to the control of cellular development and oncogenesis. In prokaryotes, the function of pervasive transcription and its output on cell physiology is still unknown. Most bacteria possess termination factor Rho, which represses pervasive, mostly antisense, transcription. Here, we investigate the biological significance of Rho-controlled transcription in the Gram-positive model bacterium Bacillus subtilis. Rho inactivation strongly affected gene expression in B. subtilis, as assessed by transcriptome and proteome analysis of a rho–null mutant during exponential growth in rich medium. Subsequent physiological analyses demonstrated that a considerable part of Rho-controlled transcription is connected to balanced regulation of three mutually exclusive differentiation programs: cell motility, biofilm formation, and sporulation. In the absence of Rho, several up-regulated sense and antisense transcripts affect key structural and regulatory elements of these differentiation programs, thereby suppressing motility and biofilm formation and stimulating sporulation. We dissected how Rho is involved in the activity of the cell fate decision-making network, centered on the master regulator Spo0A. We also revealed a novel regulatory mechanism of Spo0A activation through Rho-dependent intragenic transcription termination of the protein kinase kinB gene. Altogether, our findings indicate that distinct Rho-controlled transcripts are functional and constitute a previously unknown built-in module for the control of cell differentiation in B. subtilis. In a broader context, our results highlight the recruitment of the termination factor Rho, for which the conserved biological role is probably to repress pervasive transcription, in highly integrated, bacterium-specific, regulatory networks.
Highlights
Transcription provides the basis for cellular development and metabolism in all living organisms by allowing the expression of the information stored in the DNA sequence of the genes
We reanalyzed the dataset of genome-wide expression profiles previously established for B. subtilis 168 derivative strain 1012 and its isogenic rho mutant (RM) grown exponentially in rich medium as a starting point for dissecting the pathways by which the absence of Rho could affect B. subtilis physiology [17]
The previous analysis of the RM strain was mainly focused on the detection of transcription outside of the transcribed regions (TRs) detected in the wild type strain [17]
Summary
Transcription provides the basis for cellular development and metabolism in all living organisms by allowing the expression of the information stored in the DNA sequence of the genes. The phenomenon of pervasive transcription raised questions concerning the biological functions of the associated RNA species This potentially futile process could have deleterious effects on cell physiology by interfering with sense transcription or chromosome replication or by compromising genome stability or cellular energy status [5,6,7]. Turning it completely off may be difficult and counterproductive from an evolutionary stand-point, since mutations can continuously create new transcription initiation sites or alter the termination of existing transcription units. The produced non-coding RNAs (ncRNAs) are involved in a wide range of cellular processes, playing crucial roles in development, aging, disease, and the evolution of complex organisms [7, 12, 13]
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