SymE-SymR toxin-antitoxin system

SymR was originally labelled RyjC and is a 77 nucleotide (nt) RNA with a σ⁷⁰ promoter. RyjC was found to overlap the yjiW open reading frame on the opposite strand by 6 nt, and was characterized as an antisense RNA which bound the 5' untranslated region of yjiW.{{cite journal | vauthors = Kawano M, Reynolds AA, Miranda-Rios J, Storz G | title = Detection of 5'- and 3'-UTR-derived small RNAs and cis-encoded antisense RNAs in Escherichia coli | journal = Nucleic Acids Research | volume = 33 | issue = 3 | pages = 1040–50 | year = 2005 | pmid = 15718303 | pmc = 549416 | doi = 10.1093/nar/gki256 }} Further study led to the renaming of both yjiW and RyjC to SymE (SOS-induced yjiW gene with similarity to [https://www.uniprot.org/uniprot/P0AE72 MazE]) and SymR, respectively. Despite similarities to the AbrB superfamily, the SymE family has been exclusively found in proteobacteria.

The SymR antisense RNA is transcribed 3 nt behind the SymE start codon which is why the SymR promoter is considered embedded within the SymE codon. As a result, SymR blocks RNA translation of SymE by antisense binding, suggesting that this ultimately leads to SymR mRNA degradation.{{cite journal | vauthors = Fozo EM, Hemm MR, Storz G | title = Small toxic proteins and the antisense RNAs that repress them | journal = Microbiology and Molecular Biology Reviews | volume = 72 | issue = 4 | pages = 579–89, Table of Contents | date = December 2008 | pmid = 19052321 | pmc = 2593563 | doi = 10.1128/MMBR.00025-08 }} Amino acid analysis has concluded that SymE may have evolved into an RNA cleavage protein that exhibits toxin-like behavior due to transcription factors or antitoxins. In contrast to other common toxin-antitoxin systems, the SymR antitoxin is more stable than the SymE toxin.

Following DNA damage, the SOS response represses transcription of SymR RNA, allowing SymE toxin to degrade potentially damaged mRNA until DNA has been repaired. Conversely, SymE is tightly repressed by LexA repressor binding sites, SymR, and the Lon protease. These three factors are present at multiple levels where LexA is involved in transcription downregulation, SymR RNA is involved in translation downregulation, and Lon protease is involved in protein degradation. The extent of repression on SymE is dependent on the additive power of LexA, SymR, and Lon protease. Overall, SymE synthesis is slow since its activity is highly dependent on DNA repair proteins. In the cellular environment, mitomycin C damages DNA which leads to an overexpression of SymE mRNA to initiate DNA repair.{{cite journal | vauthors = Brielle R, Pinel-Marie ML, Felden B | title = Linking bacterial type I toxins with their actions | journal = Current Opinion in Microbiology | volume = 30 | pages = 114–121 | date = April 2016 | pmid = 26874964 | doi = 10.1016/j.mib.2016.01.009 | series = Cell regulation | url = https://www.hal.inserm.fr/inserm-01274292/file/Linking%20bacterial%20type%20I%20toxins%20with%20their%20actions_accepted.pdf }}

The overexpression of SymE demonstrated negative effects on the growth of colony-forming cells when tested in vitro. SymE exhibits its toxicity by repressing global translation within the cell, cleaving mRNA in a similar manner to [https://www.uniprot.org/uniprot/P0AE70 MazF], another toxin.{{cite journal | vauthors = Gerdes K, Wagner EG | title = RNA antitoxins | journal = Current Opinion in Microbiology | volume = 10 | issue = 2 | pages = 117–24 | date = April 2007 | pmid = 17376733 | doi = 10.1016/j.mib.2007.03.003 }} Quantitative Northern blot experiments showed that SymR RNA is present in cells at 10 times the concentration of SymE mRNA (0.02 fmol μg⁻¹ and 0.2 fmol μg⁻¹).

The SymE toxin consists of 113 amino acids. When evaluating the amino acid sequence and tertiary structure of SymE, strong similarities were found which resemble the [https://pfam.xfam.org/clan/AbrB AbrB] superfamily. This superfamily mainly functions as transcription factors or antitoxins; however, the similarity of SymE to the primary sequence and tertiary structure of the AbrB superfamily suggests that SymE proteins experienced an evolutionary shift from a transcription factor or antitoxin to a RNA-associating protein that exhibits toxin behavior. Between the AbrB superfamily protein structure and the SymE protein structure, there are several key hydrophobic residues that are highly conserved in the $\backslash alpha$-helix at the center of the protein as well as the $\backslash beta$ strand-1. Despite these key similarities, SymE exhibits polar residues not found in the general structure of the AbrB superfamily, indicating that these residues may have a role in the SymE RNA cleavage ability.

[https://swissmodel.expasy.org/ SWISS-MODEL] contains more than several experimental structures and theoretical homology models that define certain aspects of the SymE primary sequence and tertiary structure. The UniProtKB accession number [https://swissmodel.expasy.org/repository/uniprot/P39394 P39394] indicates the general structure of the SymE toxin in Escherichia coli (strain K12).{{Cite web|title=UniProtKB - P39394 (SYME_ECOLI)|url=https://www.uniprot.org/uniprot/P39394|last=The UniProt Consortium|date=2020|website=uniprot.org|url-status=live|archive-url=https://www.uniprot.org/uniprot/P39394?version=*|archive-date=10 July 2007|access-date=4 May 2020}} In the SWISS-MODEL SymE theoretical model, the $\backslash alpha$-helix contains amino acids G44, Q45, W46, L47, E48, A49, and A50.{{cite journal | vauthors = Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, Heer FT, de Beer TA, Rempfer C, Bordoli L, Lepore R, Schwede T | display-authors = 6 | title = SWISS-MODEL: homology modelling of protein structures and complexes | journal = Nucleic Acids Research | volume = 46 | issue = W1 | pages = W296–W303 | date = July 2018 | pmid = 29788355 | pmc = 6030848 | doi = 10.1093/nar/gky427 }}{{cite journal | vauthors = Guex N, Peitsch MC, Schwede T | title = Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer: a historical perspective | journal = Electrophoresis | volume = 30 Suppl 1 | issue = S1 | pages = S162-73 | date = June 2009 | pmid = 19517507 | doi = 10.1002/elps.200900140 | s2cid = 39507113 }}{{cite journal | vauthors = Bienert S, Waterhouse A, de Beer TA, Tauriello G, Studer G, Bordoli L, Schwede T | title = The SWISS-MODEL Repository-new features and functionality | journal = Nucleic Acids Research | volume = 45 | issue = D1 | pages = D313–D319 | date = January 2017 | pmid = 27899672 | pmc = 5210589 | doi = 10.1093/nar/gkw1132 }}{{cite journal | vauthors = Studer G, Rempfer C, Waterhouse AM, Gumienny R, Haas J, Schwede T | title = QMEANDisCo-distance constraints applied on model quality estimation | journal = Bioinformatics | volume = 36 | issue = 8 | pages = 2647 | date = April 2020 | pmid = 32048708 | pmc = 7178391 | doi = 10.1093/bioinformatics/btaa058 }}{{cite journal | vauthors = Bertoni M, Kiefer F, Biasini M, Bordoli L, Schwede T | title = Modeling protein quaternary structure of homo- and hetero-oligomers beyond binary interactions by homology | journal = Scientific Reports | volume = 7 | issue = 1 | pages = 10480 | date = September 2017 | pmid = 28874689 | pmc = 5585393 | doi = 10.1038/s41598-017-09654-8 | bibcode = 2017NatSR...710480B }} The $\backslash beta$ strand-1 contains amino acids G55, T56, A57, V58, D59, V60, K61, V62, I67, V68, L69, T70, A71, Q72, P73, and P74 with the $\backslash beta$-turn containing M63, E64, G65, and C66.

SymR is an antisense RNA meaning its secondary structure has characteristic stem-and-loop elements as well as unpaired regions flanking the structure.{{cite book | first1 = Sydney X | last1 = Brenner | first2 = Jeffrey H | last2 = Miller | name-list-style = vanc |title=Encyclopedia of genetics |isbn=0-12-227080-0|location=San Diego|oclc=48655705}} The predicted secondary structure of SymR showcases a loop containing the nucleotide sequence CCAG. This characteristic loop is shared with the lstR-1 and OhsC RNA proteins and is predicted to be a binding site for other proteins. Currently, there are no known files on the [https://www.rcsb.org/ RCSB protein data bank] or [https://swissmodel.expasy.org/repository SWISS-MODEL repository] that indicate a predicted tertiary structure of SymR.

• Toxin-antitoxin system
• Hok/sok system

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• {{Rfam|id=RF01809|name=SymR antitoxin}}

Category:Antisense RNA

Category:RNA antitoxins