The hok/sok system is a postsegregational killing mechanism employed by the R1 plasmid in Escherichia coli. It was the first type I toxin-antitoxin pair to be identified through characterisation of a plasmid-stabilising locus. [1] It is a type I system because the toxin is neutralised by a complementary RNA, rather than a partnered protein (type II toxin-antitoxin). [2]
The hok/sok system features two transcripts:
The hok (host killing) gene of the mRNA encodes a toxic transmembrane protein. The hok and mok (modulation of killing) protein-coding regions in the mRNA are partially overlapping, and their translation is coupled, such that the ribosome first translates the mok reading frame and then slides back to translate the hok gene. [3] The sok (suppression of killing) antisense RNA is complementary to a portion of the mRNA corresponding to the hok 5' untranslated region and the mok translation initiation region (TIR). Upon binding to the hok/mok mRNA, sok inhibits translation of the Mok protein and thus indirectly prevents translation of the Hok protein toxin. [4]
The full-length hok mRNA is stable ( half-life 20 minutes), while the sok RNA is short lived (half-life 30 seconds).
HOK | |||||||||
---|---|---|---|---|---|---|---|---|---|
Identifiers | |||||||||
Symbol | HOK | ||||||||
Pfam | PF01848 | ||||||||
InterPro | IPR000021 | ||||||||
PROSITE | PDOC00481 | ||||||||
|
Hok mRNA is found in two forms:
The full-length hok transcript is highly structured and immune to both ribosome binding (which initiates Hok toxin translation) and sok antisense binding (which leads to degradation of both transcripts). The full-length hok transcript is slowly processed - 39 nucleotides are cleaved from the 3' end of the molecule. Processing initiates drastic structural rearrangments in the hok transcript, such that the ribosome and sok RNA binding sites become accessible. [5]
When E. coli undergoes cell division, the two daughter cells inherit the stable full-length hok mRNA from the parent cell. While daughter cells also inheret sok RNA antitoxin, due to their short half-life these molecules quickly degrade. [6] Meanwhile, the full-length hok mRNA is slowly processed to the truncated active form.
If a daughter cell has inherited the R1 plasmid, it has inherited the sok gene, which has a strong promoter that brings about high levels of transcription. [7] The newly transcribed Sok RNA then inhibits the translation of Hok protein by binding to the active truncated mRNA. The sok transcript forms a duplex with the leader region of the truncated hok mRNA and this is recognized by RNase III and degraded. The cleavage products are very unstable and soon decay. [8]
Daughter cells without a copy of the R1 plasmid die because they do not have the means to produce more sok antitoxin transcript to inhibit translation of the inherited hok mRNA. The killing system is said to be postsegregational (PSK), [9] since cell death occurs after segregation of the plasmid. [10] [11]
During transcription of the hok mRNA, the ribosome and sok binding sites emerge from the transcriptional machinery before the stable full-length structure can form. Nevertheless, premature translation and degredation are prevented by the formation of transient structures which sequester these binding sites until the molecule is fully synthesized. [12]
The hok gene codes for a 52 amino acid toxic protein which causes cell death by depolarization of the cell membrane. [13] [14] It works in a similar way to holin proteins which are produced by bacteriophages before cell lysis. [2] [15]
hok/sok homologues denoted flmA/B (FlmA is the protein toxin and FlmB RNA the antisense regulator) [16] are carried on the F plasmid which operate in the same way to maintain the stability of the plasmid. [17] The F plasmid contains another homologous toxin-antitoxin system called srnB. [13]
The first type I toxin-antitoxin system to be found in gram-positive bacteria is the RNAI-RNAII system of the pAD1 plasmid in Enterococcus faecalis. Here, RNAI encodes a toxic protein Fst while RNAII is the regulatory sRNA. [18]
In E. coli strain K-12 there are four long direct repeats (ldr) which encode short open reading frames of 35 codons organised in a homologous manner to the hok/sok system. One of the repeats encodes LdrD, a toxic protein which causes cell death. An unstable antisense RNA regulator (Rd1D) blocks the translation of the LdrD transcript. [19] A mok homologue which overlaps each ldr loci has also been found. [6]
IstR RNA works in a similar system in conjunction with the toxic TisB protein. [20]
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link){{DEFAULTSORT:Hok/Sok System}} [[Category:Bacteriology]] [[Category:Escherichia coli]] [[Category:RNA antitoxins]]
The hok/sok system is a postsegregational killing mechanism employed by the R1 plasmid in Escherichia coli. It was the first type I toxin-antitoxin pair to be identified through characterisation of a plasmid-stabilising locus. [1] It is a type I system because the toxin is neutralised by a complementary RNA, rather than a partnered protein (type II toxin-antitoxin). [2]
The hok/sok system features two transcripts:
The hok (host killing) gene of the mRNA encodes a toxic transmembrane protein. The hok and mok (modulation of killing) protein-coding regions in the mRNA are partially overlapping, and their translation is coupled, such that the ribosome first translates the mok reading frame and then slides back to translate the hok gene. [3] The sok (suppression of killing) antisense RNA is complementary to a portion of the mRNA corresponding to the hok 5' untranslated region and the mok translation initiation region (TIR). Upon binding to the hok/mok mRNA, sok inhibits translation of the Mok protein and thus indirectly prevents translation of the Hok protein toxin. [4]
The full-length hok mRNA is stable ( half-life 20 minutes), while the sok RNA is short lived (half-life 30 seconds).
HOK | |||||||||
---|---|---|---|---|---|---|---|---|---|
Identifiers | |||||||||
Symbol | HOK | ||||||||
Pfam | PF01848 | ||||||||
InterPro | IPR000021 | ||||||||
PROSITE | PDOC00481 | ||||||||
|
Hok mRNA is found in two forms:
The full-length hok transcript is highly structured and immune to both ribosome binding (which initiates Hok toxin translation) and sok antisense binding (which leads to degradation of both transcripts). The full-length hok transcript is slowly processed - 39 nucleotides are cleaved from the 3' end of the molecule. Processing initiates drastic structural rearrangments in the hok transcript, such that the ribosome and sok RNA binding sites become accessible. [5]
When E. coli undergoes cell division, the two daughter cells inherit the stable full-length hok mRNA from the parent cell. While daughter cells also inheret sok RNA antitoxin, due to their short half-life these molecules quickly degrade. [6] Meanwhile, the full-length hok mRNA is slowly processed to the truncated active form.
If a daughter cell has inherited the R1 plasmid, it has inherited the sok gene, which has a strong promoter that brings about high levels of transcription. [7] The newly transcribed Sok RNA then inhibits the translation of Hok protein by binding to the active truncated mRNA. The sok transcript forms a duplex with the leader region of the truncated hok mRNA and this is recognized by RNase III and degraded. The cleavage products are very unstable and soon decay. [8]
Daughter cells without a copy of the R1 plasmid die because they do not have the means to produce more sok antitoxin transcript to inhibit translation of the inherited hok mRNA. The killing system is said to be postsegregational (PSK), [9] since cell death occurs after segregation of the plasmid. [10] [11]
During transcription of the hok mRNA, the ribosome and sok binding sites emerge from the transcriptional machinery before the stable full-length structure can form. Nevertheless, premature translation and degredation are prevented by the formation of transient structures which sequester these binding sites until the molecule is fully synthesized. [12]
The hok gene codes for a 52 amino acid toxic protein which causes cell death by depolarization of the cell membrane. [13] [14] It works in a similar way to holin proteins which are produced by bacteriophages before cell lysis. [2] [15]
hok/sok homologues denoted flmA/B (FlmA is the protein toxin and FlmB RNA the antisense regulator) [16] are carried on the F plasmid which operate in the same way to maintain the stability of the plasmid. [17] The F plasmid contains another homologous toxin-antitoxin system called srnB. [13]
The first type I toxin-antitoxin system to be found in gram-positive bacteria is the RNAI-RNAII system of the pAD1 plasmid in Enterococcus faecalis. Here, RNAI encodes a toxic protein Fst while RNAII is the regulatory sRNA. [18]
In E. coli strain K-12 there are four long direct repeats (ldr) which encode short open reading frames of 35 codons organised in a homologous manner to the hok/sok system. One of the repeats encodes LdrD, a toxic protein which causes cell death. An unstable antisense RNA regulator (Rd1D) blocks the translation of the LdrD transcript. [19] A mok homologue which overlaps each ldr loci has also been found. [6]
IstR RNA works in a similar system in conjunction with the toxic TisB protein. [20]
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link){{DEFAULTSORT:Hok/Sok System}} [[Category:Bacteriology]] [[Category:Escherichia coli]] [[Category:RNA antitoxins]]