# Cellular Self-Digestion and Persistence in Bacteria
## 4 Intracellular Degradation Mechanisms
### RNA Degradation  
RNases comprise a group of hydrolytic enzymes that degrade RNA into smaller components [68]. There are two main types of ribonucleases: endoribonucleases (e.g., RNase P, III, BN, HI/II, I, E, G, and LS) and exoribonucleases (e.g., RNase D, T, PH, R and II, and PNPage) [68; 156]. Endoribonucleases cleave single-stranded RNAs (ssRNA) or double-stranded RNAs (dsRNAA) at internal phosphodiester bonds, whereas exoribonucleases cleave either the \(3^{\prime}\) end or \(5^{\prime}\) end of an RNA molecule [157; 156]. In addition to their ability to degrade RNA, RNases play diverse roles in RNA metabolism, functioning in RNA maturation, quality control, and regulation [68]. RNases from different bacteria are generally conserved; however, some RNases can be species-specific, such as the _B. subtilis_ RNase MS (55 rRNA maturation), which is not present in _E. coli_[158]. Degradation of stable RNAs via the action of RNases occurs in response to depletion of nutrient sources during starvation [159]. As ribosomes account for the majority of RNAs in a cell, the RNAs degraded in this process are primarily ribosomal RNAs (rRNAs). These molecules are plentiful in cells and store substantial amounts of nutrients and energy that can be consumed during starvation [160]. For example, approximately 90% of 23S rRNA and 50% of 16S rRNA are degraded in _Salmonella_ strains upon entry into the stationary phase in Luria-Bertani cultures [69]. Transfer RNAs (tRNAs) were found to be more stable in _E. coli_ cells during phosphate starvation in a minimal medium [153]. Further, under starvation conditions, more than 70% of rRNA produced remains unused by ribosomes and is degraded in _E. coli_[161], suggesting the presence of a conserved molecular mechanism for rRNA degradation. Cells experiencing starvation from specific nutrients, such as carbon [162], nitrogen [163], phosphate [72], and magnesium (II) [164], may digest their rRNAs at different rates [153; 160], although the exact extent of rRNA degradation under starvation conditions remains poorly understood. _E. coli_ may digest their ribosomes in a unique manner, and once degradation begins, the 30S ribosomal subunit seems to perish quicker than the 50S subunit [153]. [PERSON] and [PERSON] demonstrated that in starved cells, ribosomal degradation proceeds from polysomes to ribosomal subunits [160]. The RNA pieces produced by this process are then further degraded to nucleotides by RNase II and PNPage [160]. Although ribosome dimerization and complex formation with their associated proteins has recently been shown to play a critical role in the resuscitation of rifampicin-induced antibiotic-tolerant cells [63; 165; 166], a direct correlation between the ability of mutant strains (exhibiting different RNase activities) to recover from starvation and their capacity to degrade RNA has been long established [160]. Specifically, strains that rapidly degrade RNA survive starvation better than more slowly degrading strains [160], suggesting a link between RNase activity and persister formation. RNases associated with type II TA systems, such as MqsR/MqsA [167], MazF/MazE [168], RelE/RelB [169], YoeB/YefM [34], and YafQ/Dinj [170], have been well-studied in the field of persister research. TA systems contain pairs of genes, one of which encodes a stable toxin and another that encodes an unstable antitoxin [171]. Antitoxins, under normal growth conditions, degrade, neutralize, or inhibit the associated toxin molecule [171]. Although the deletion of type II toxin molecules or TA systems, including _chpB_, _mazF_, _relB/relE_, _yefM/yoeB_, _dinfJ/yafQ_, _higB/higA_, _prlF/yhaV_, _yafN/O_, _mqgR/mqA_, and _hicicA/hicB_, does not affect bacterial persistence [172], it is well established that toxins can induce cell cycle arrest by disrupting various cellular processes [171; 173; 174]. One of the first TA systems to be associated with persistence was the HipA/HipB system.