Post-transcriptional Regulation of the Streptomyces coelicolor Stress Responsive Sigma Factor, SigH, Involves Translational Control, Proteolytic Processing, and an Anti-sigma Factor Homolog

Abstract

The sigH gene encodes a sigma factor whose transcription is controlled by stress regulatory systems and the developmental program in Streptomyces coelicolor. Here, we describe developmentally regulated post-transcriptional control systems for SigH. sigH is expressed as three primary translation products, SigH-σ37, SigH-σ51, and SigH-σ52. In vitro, SigH-σ52 was comparable to SigH-σ37 in its ability to associate with RNA polymerase core enzyme and specifically initiate transcription in vitro. While SigH-σ51/52 were the primary gene products observed throughout early phases of growth, their abundance decreased during later stages in liquid or solid phase cultures while levels of shorter, C-terminally encoded products increased. These included SigH-σ37, a product of the downstream translational initiation site, as well as two proteolytic derivatives of SigH-σ51/52 (34kDa and 38kDa). Accumulation of SigH-σ37 and processing of SigH-σ51/52 into these stable 34kDa and 38kDa derivatives correlated with morphological changes on solid medium and physiological maturation in liquid medium. SigH-σ51/52 processing did not occur on medium non-permissive for aerial mycelium formation or in one particular developmental mutant (brgA). The proteolytic activity could be detected in vitro using crude extracts of stationary phase cultures, but was absent from exponential phase cultures. prsH, the gene upstream of sigH having sequence similarity to known anti-sigma factors, was able to bind to, and thus presumably inactivate SigH-σ52, SigH-σ51, and SigH-σ37. We have shown elsewhere that prsH was conditionally required for colonial development. Thus, while at least one transcriptional regulator is known to bring about the accumulation of sigH mRNA at different times and different locations in colonies, the post-transcriptional processes described here regulate the activity of different SigH isoforms and program their temporal accumulation pattern, i.e. the elimination of SigH-σ51/52 and accumulation of SigH-σ37-like proteins, as a function of development.