Novel prokaryotic sensing and regulatory system employing previously unknown nucleic acids-based receptors

Abstract

The present study describes a previously unknown universal signaling and regulatory system, which we named TETZ-receptor system. This system is responsible for sensing, remembering, and regulating cell responses to various chemical, physical or biological stimuli. It controls cell survival, variability, reproduction, adaptation, genome changes, and gene transfer. Importantly, the TETZ-receptor system is responsible for the formation and maintenance of cell memory, as well the ability to forget preceding events. The system is composed of DNA- and RNA-based receptors located outside the membrane named TezRs, as well as reverse transcriptases and integrases. The sensory and regulatory functions of TezRs enable the TETZ-receptor system to control all major aspects of bacterial behavior, such as growth, biofilm formation and dispersal, utilization of nutrients including xenobiotics, virulence, chemo- and magnetoreception, response to external factors (e.g., temperature, UV, light and gas content), mutation events, phage-host interaction and recombination activity. Additionally, it supervises the function of other receptor-mediated signaling pathways.

Novel Cell Receptor System of Eukaryotes Formed by Previously Unknown Nucleic Acid-Based Receptors

“…Therefore, we discovered, for the first time, that the TR-system controls memory to preceding events and forgetting, which could lead to future studies on cellular programming, which has recently attracted much attention [47,132]. Notably, a similar role of TezRs in memory formation and forgetting was observed in prokaryotes [51]. Such an adaptive memory of cells to a nutrient factor is similar to the adaptive strategy of B-cells, for which the secondary and more pronounced response is based on their affinity for antigens and the higher number of cells possessing relevant receptors [134][135][136].…”

“…Here, we describe for the first time a newly discovered global TR-system in uni-and multicellular eukaryotes of different kingdoms that orchestrates major vital functions and responses and shares similarity with the identical system that we have recently identified in procaryotes [51]. This system is formed by nucleic acid-based receptors named TezRs and includes the work of reverse transcriptases and integrases.…”

“…Our previous studies demonstrated that TezRs could control the interaction between bacteriophages and bacterial hosts [51]. To confirm that TezRs could also control the interaction between viruses and eukaryotic cells and further characterize this process, we determined that the destruction of TezRs could inhibit viral replication.…”

“…Control probes were treated with water used as a vehicle for nucleases, and cells were placed in 2 mL microcentrifuge tubes (Axygen Scientific Inc., Union City, CA) at 5.5 log10 CFU/mL. Each tube was heated to 37,50,51,52,53,54,55,56,57,58, or 59 • C in a dry bath (Corning, LSE, Digital Dry Bath) for 15 min. After heating, some control C. albicans probes were immediately treated with nucleases to destroy primary TezRs or with water used as a vehicle for nucleases and washed three times to remove nucleases, as previously discussed.…”

“…Taking a broad range of stimuli whose reception cannot be well explained with known receptors we studied the receptive and regulatory roles of extracellular DNA and RNA, since the novel roles, of nucleic acids that go beyond the processing of genetic information and protein synthesis, including the interaction with proteins, were recently described [48][49][50]. We discovered that prokaryotes have a previously unknown receptive system that is responsible for the interaction of cells with the environment [51]. Here, we show the existence of a similar, previously unknown TR-receptive system in eukaryotes that manages interactions between cells and the environment.…”