DsrA RNA

Last updated
DsrA RNA
RF00014.jpg
Identifiers
SymbolDsrA
Rfam RF00014
Other data
RNA type Gene; sRNA
Domain(s) Bacteria
SO SO:0000378
PDB structures PDBe

DsrA RNA is a non-coding RNA that regulates both transcription, by overcoming transcriptional silencing by the nucleoid-associated H-NS protein, [1] and translation, by promoting efficient translation of the stress sigma factor, RpoS. [2] [3] These two activities of DsrA can be separated by mutation: the first of three stem-loops of the 85 nucleotide RNA is necessary for RpoS translation but not for anti-H-NS action, while the second stem-loop is essential for antisilencing and less critical for RpoS translation. The third stem-loop, which behaves as a transcription terminator, can be substituted by the trp transcription terminator without loss of either DsrA function. The sequence of the first stem-loop of DsrA is complementary with the upstream leader portion of RpoS messenger RNA, suggesting that pairing of DsrA with the RpoS message might be important for translational regulation. The structures of DsrA and DsrA/rpoS complex were studied by NMR. The study concluded that the sRNA contains a dynamic conformational equilibrium for its second stem–loop which might be an important mechanism for DsrA to regulate the translations of its multiple target mRNAs. [4]

Contents

There is evidence that DsrA RNA can self-assemble into nanostructures through antisense interactions of three self-complementary regions. [5] [6]

Targets of DsrA

There is experimental evidence to suggest that DsrA interacts with the protein-coding genes hns, [7] [8] [9] rbsD, [7] argR, [7] ilvI [7] and rpoS [10] [11] [12] [13] via an anti-sense mechanism.

DsrA folds into a structure with three hairpins. The second of these (nucleotides 23–60) binds to Hfq. [14]

Related Research Articles

The gene rpoS encodes the sigma factor sigma-38, a 37.8 kD protein in Escherichia coli. Sigma factors are proteins that regulate transcription in bacteria. Sigma factors can be activated in response to different environmental conditions. rpoS is transcribed in late exponential phase, and RpoS is the primary regulator of stationary phase genes. RpoS is a central regulator of the general stress response and operates in both a retroactive and a proactive manner: it not only allows the cell to survive environmental challenges, but it also prepares the cell for subsequent stresses (cross-protection). The transcriptional regulator CsgD is central to biofilm formation, controlling the expression of the curli structural and export proteins, and the diguanylate cyclase, adrA, which indirectly activates cellulose production. The rpoS gene most likely originated in the gammaproteobacteria.

DicF RNA

DicF RNA is a non-coding RNA that is an antisense inhibitor of cell division gene ftsZ. DicF is bound by the Hfq protein which enhances its interaction with its targets. Pathogenic E. coli strains possess multiple copies of sRNA DicF in their genomes, while non-pathogenic strains do not. DicF and Hfq are both necessary to reduce FtsZ protein levels, leading to cell filamentation under anaerobic conditions.

GcvB RNA

The gcvB RNA gene encodes a small non-coding RNA involved in the regulation of a number of amino acid transport systems as well as amino acid biosynthetic genes. The GcvB gene is found in enteric bacteria such as Escherichia coli. GcvB regulates genes by acting as an antisense binding partner of the mRNAs for each regulated gene. This binding is dependent on binding to a protein called Hfq. Transcription of the GcvB RNA is activated by the adjacent GcvA gene and repressed by the GcvR gene. A deletion of GcvB RNA from Y. pestis changed colony shape as well as reducing growth. It has been shown by gene deletion that GcvB is a regulator of acid resistance in E. coli. GcvB enhances the ability of the bacterium to survive low pH by upregulating the levels of the alternate sigma factor RpoS. A polymeric form of GcvB has recently been identified. Interaction of GcvB with small RNA SroC triggers the degradation of GcvB by RNase E, lifting the GcvB-mediated mRNA repression of its target genes.

OmrA-B RNA

The OmrA-B RNA gene family is a pair of homologous OmpR-regulated small non-coding RNA that was discovered in E. coli during two large-scale screens. OmrA-B is highly abundant in stationary phase, but low levels could be detected in exponentially growing cells as well. RygB is adjacent to RygA a closely related RNA. These RNAs bind to the Hfq protein and regulate gene expression by antisense binding. They negatively regulate the expression of several genes encoding outer membrane proteins, including cirA, CsgD, fecA, fepA and ompT by binding in the vicinity of the Shine-Dalgarno sequence, suggesting the control of these targets is dependent on Hfq protein and RNase E. Taken together, these data suggest that OmrA-B participates in the regulation of outer membrane composition, responding to environmental conditions.

OxyS RNA

OxyS RNA is a small non-coding RNA which is induced in response to oxidative stress in Escherichia coli. This RNA acts as a global regulator to activate or repress the expression of as many as 40 genes, by an antisense mechanism, including the fhlA-encoded transcriptional activator and the rpoS-encoded sigma(s) subunit of RNA polymerase. OxyS is bound by the Hfq protein, that increases the OxyS RNA interaction with its target messages. Binding to Hfq alters the conformation of OxyS. The 109 nucleotide RNA is thought to be composed of three stem-loops.

RprA RNA

The RprA RNA gene encodes a 106 nucleotide regulatory non-coding RNA. Translational regulation of the stationary phase sigma factor RpoS is mediated by the formation of a double-stranded RNA stem-loop structure in the upstream region of the rpoS messenger RNA, occluding the translation initiation site.

RybB RNA

RybB is a small non-coding RNA was identified in a large scale screen of Escherichia coli. The function of this short RNA has been studied using a transcriptomic approach and kinetic analyses of target mRNA decay in vivo. RybB was identified as a factor that selectively accelerates the decay of multiple major omp mRNAs upon induction of the envelope stress response. This RNA has been shown to bind to the Hfq protein.

RyhB

RyhB RNA is a 90 nucleotide RNA that down-regulates a set of iron-storage and iron-using proteins when iron is limiting; it is itself negatively regulated by the ferric uptake repressor protein, Fur.

SgrS RNA

SgrS is a 227 nucleotide small RNA that is activated by SgrR in Escherichia coli during glucose-phosphate stress. The nature of glucose-phosphate stress is not fully understood, but is correlated with intracellular accumulation of glucose-6-phosphate. SgrS helps cells recover from glucose-phosphate stress by base pairing with ptsG mRNA and causing its degradation in an RNase E dependent manner. Base pairing between SgrS and ptsG mRNA also requires Hfq, an RNA chaperone frequently required by small RNAs that affect their targets through base pairing. The inability of cells expressing sgrS to create new glucose transporters leads to less glucose uptake and reduced levels of glucose-6-phosphate. SgrS is an unusual small RNA in that it also encodes a 43 amino acid functional polypeptide, SgrT, which helps cells recover from glucose-phosphate stress by preventing glucose uptake. The activity of SgrT does not affect the levels of ptsG mRNA of PtsG protein. It has been proposed that SgrT exerts its effects through regulation of the glucose transporter, PtsG.

MicA RNA

The MicA RNA is a small non-coding RNA that was discovered in E. coli during a large scale screen. Expression of SraD is highly abundant in stationary phase, but low levels could be detected in exponentially growing cells as well.

ArcZ RNA

In molecular biology the ArcZ RNA is a small non-coding RNA (ncRNA). It is the functional product of a gene which is not translated into protein. ArcZ is an Hfq binding RNA that functions as an antisense regulator of a number of protein coding genes.

Hfq protein

The Hfq protein encoded by the hfq gene was discovered in 1968 as an Escherichia coli host factor that was essential for replication of the bacteriophage Qβ. It is now clear that Hfq is an abundant bacterial RNA binding protein which has many important physiological roles that are usually mediated by interacting with Hfq binding sRNA.

IscR stability element

The IscR stability element is a conserved secondary structure found in the intergenic regions of iscRSUA polycistronic mRNA. This secondary structure prevents the degradation of the iscR mRNA.

rpoS mRNA encodes for the rpoS stress factor, sigma S in Escherichia coli and related bacteria, where DsrA in conjunction with the Sm like RNA binding protein, Hfq promote the translation of this rpoS mRNA. The 5′ UTR of the rpoS mRNA forms a self-inhibitory stem loop that shields the shine-dalgarno sequence and therefore inhibits translation. The secondary structure of the 5′UTR was predicted by acetylation of ribose 2′-hydroxyls with NMIA and by using a secondary structure prediction program, RNAstructure. DsrA stimulates rpoS translation by binding in the 5′UTR and causes the stem loop to open, exposing the ribosome binding site.

MicX sRNA

MicX sRNA is a small non-coding RNA found in Vibrio cholerae. It was given the name MicX as it has a similar function to MicA, MicC and MicF in E. coli. MicX sRNA negatively regulates an outer membrane protein and also a component of an ABC transporter. These interactions were predicted and then confirmed using a DNA microarray.

CspA mRNA 5′ UTR

cspA mRNA 5' UTR is the untranslated region of the cspA gene, which is important in the cold shock response in Enterobacteriales such as E. coli. The 5' UTR element acts as an RNA thermometer, regulating the expression of cspA in response to temperature. By regulating temperature, cspA proteins carry out the vital function of homeostasis.

Bacterial small RNAs (sRNA) are small RNAs produced by bacteria; they are 50- to 500-nucleotide non-coding RNA molecules, highly structured and containing several stem-loops. Numerous sRNAs have been identified using both computational analysis and laboratory-based techniques such as Northern blotting, microarrays and RNA-Seq in a number of bacterial species including Escherichia coli, the model pathogen Salmonella, the nitrogen-fixing alphaproteobacterium Sinorhizobium meliloti, marine cyanobacteria, Francisella tularensis, Streptococcus pyogenes, the pathogen Staphylococcus aureus, and the plant pathogen Xanthomonas oryzae pathovar oryzae. Bacterial sRNAs affect how genes are expressed within bacterial cells via interaction with mRNA or protein, and thus can affect a variety of bacterial functions like metabolism, virulence, environmental stress response, and structure.

The gene rpoE encodes the sigma factor sigma-24, a protein in Escherichia coli and other species of bacteria. Depending on the bacterial species, this gene may be referred to as sigE.

Susan Gottesman American microbiologist

Susan Gottesman is microbiologist at the National Cancer Institute (NCI), which is part of the National Institutes of Health. She is a pioneer in the area of biological regulation in which enzymes that destroy specific other proteins, called proteases, play a central role inside the cell. She discovered and elucidated the central features of a new family of proteases that require energy for their function in the form of ATP-hydrolysis. She has also played a major role in the discovery and characterization of bacterial small RNAs.

Bacterial small RNAs (sRNA) are an important class of regulatory molecules in bacteria such as Brucella. They are often bound to the chaperone protein Hfq, which allows them to interact with mRNA(s). In Brucella suis 1330 RNA sequencing identified a novel list of 33 sRNAs and 62 Hfq-associated mRNAs. In Brucella melitensis eight novel sRNA genes were identified using bioinformatic and experimental approach. One of them BSR0602 was found to modulate the intracellular survival of B. melitensis. In another large-scale deep sequencing study 1321 sRNAs were identified in B. melitensis. BSR0441 sRNA was further investigated in this study and shown to play role in the intracellular survival. sRNA BM-sr0117 from Brucella melitensis was identified and shown to be bound to and cleaved by Bm-RNase III. AbcR and AbcR2 were studied B. abortus. Seven novel sRNAs were validated and their interaction with a putative target sequence was verified in B. abortus.

References

  1. Sledjeski, D; Gottesman S (1995). "A small RNA acts as an antisilencer of the H-NS-silenced rcsA gene of Escherichia coli". Proc Natl Acad Sci USA. 92 (6): 2003–2007. Bibcode:1995PNAS...92.2003S. doi: 10.1073/pnas.92.6.2003 . PMC   42411 . PMID   7534408.
  2. Majdalani, N; Cunning C; Sledjeski D; Elliott T; Gottesman S (1998). "DsrA RNA regulates translation of RpoS message by an anti-antisense mechanism, independent of its action as an antisilencer of transcription". Proc Natl Acad Sci USA. 95 (21): 12462–12467. Bibcode:1998PNAS...9512462M. doi: 10.1073/pnas.95.21.12462 . PMC   22853 . PMID   9770508.
  3. Gottesman, S (2005). "Micros for microbes: non-coding regulatory RNAs in bacteria". Trends Genet. 21 (7): 399–404. CiteSeerX   10.1.1.391.8944 . doi:10.1016/j.tig.2005.05.008. PMID   15913835.
  4. Wu, Pengzhi; Liu, Xiaodan; Yang, Lingna; Sun, Yitong; Gong, Qingguo; Wu, Jihui; Shi, Yunyu (2017-09-19). "The important conformational plasticity of DsrA sRNA for adapting multiple target regulation". Nucleic Acids Research. 45 (16): 9625–9639. doi:10.1093/nar/gkx570. ISSN   1362-4962. PMC   5766208 . PMID   28934467.
  5. Cayrol B, Nogues C, Dawid A, Sagi I, Silberzan P, Isambert H (2009). "A Nanostructure Made of a Bacterial Noncoding RNA". J Am Chem Soc. 131 (47): 17270–17276. doi:10.1021/ja906076e. PMID   19821568.
  6. Cayrol B, Geinguenaud F, Lacoste J, Busi F, Le Dérout J, Piétrement O, Le Cam E, Régnier P, Lavelle C, Arluison V (2009). "Auto-assembly of E. coli DsrA small noncoding RNA: Molecular characteristics and functional consequences." RNA Biol. 6 (4): 434–445. doi: 10.4161/rna.6.4.8949 . PMID   19535898.
  7. 1 2 3 4 Lease RA, Cusick ME, Belfort M (1998). "Riboregulation in Escherichia coli: DsrA RNA acts by RNA:RNA interactions at multiple loci". Proc Natl Acad Sci U S A. 95 (21): 12456–12461. Bibcode:1998PNAS...9512456L. doi: 10.1073/pnas.95.21.12456 . PMC   22852 . PMID   9770507.
  8. Urban JH, Vogel J (2007). "Translational control and target recognition by Escherichia coli small RNAs in vivo". Nucleic Acids Res. 35 (3): 1018–1037. doi:10.1093/nar/gkl1040. PMC   1807950 . PMID   17264113.
  9. Lease RA Belfort M (2000). "A trans-acting RNA as a control switch in Escherichia coli: DsrA modulates function by forming alternative structures". Proc Natl Acad Sci U S A. 97 (18): 9919–9924. Bibcode:2000PNAS...97.9919L. doi: 10.1073/pnas.170281497 . PMC   27626 . PMID   10954740.
  10. Majdalani N, Cunning C, Sledjeski D, Elliott T, Gottesman S (1998). "DsrA RNA regulates translation of RpoS message by an anti-antisense mechanism, independent of its action as an antisilencer of transcription". Proc Natl Acad Sci U S A. 95 (21): 12462–12467. Bibcode:1998PNAS...9512462M. doi: 10.1073/pnas.95.21.12462 . PMC   22853 . PMID   9770508.
  11. Majdalani N, Chen S, Murrow J, St John K, Gottesman S (2001). "Regulation of RpoS by a novel small RNA: the characterization of RprA". Mol Microbiol. 39 (5): 1382–1394. doi: 10.1111/j.1365-2958.2001.02329.x . PMID   11251852.
  12. Sledjeski DD, Gupta A, Gottesman S (1996). "The small RNA, DsrA, is essential for the low temperature expression of RpoS during exponential growth in Escherichia coli". EMBO J. 15 (15): 3993–4000. doi:10.1002/j.1460-2075.1996.tb00773.x. PMC   452119 . PMID   8670904.
  13. Sledjeski DD, Whitman C, Zhang A (2001). "Hfq is necessary for regulation by the untranslated RNA DsrA". J Bacteriol. 183 (6): 1997–2005. doi:10.1128/JB.183.6.1997-2005.2001. PMC   95095 . PMID   11222598.
  14. Brescia, CC; Mikulecky, PJ; Feig, AL; Sledjeski, DD (Jan 2003). "Identification of the Hfq-binding site on DsrA RNA: Hfq binds without altering DsrA secondary structure". RNA. 9 (1): 33–43. doi:10.1261/rna.2570803. PMC   1370368 . PMID   12554874.

Further reading