Natural antisense RNAs as mRNA regulatory elements in bacteria: a review on function and applications

Saberi, Fatemeh; Kamali, Mohammad; Najafi, Ali; Yazdanparast, Alavieh; Moghaddam, Mehrdad Moosazadeh

doi:10.1186/s11658-016-0007-z

Cited by 69 publications

(58 citation statements)

References 75 publications

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“…Nevertheless, antisense transcripts are known to act as genetic switches controlling bacterial competence, virulence, and regulation of toxins [ 68 – 70 ]. Additionally, several antisense RNAs are known to function as post-transcriptional inducers or inhibitors of gene expression and protein translation, and as regulators of plasmid copy numbers through inhibition of primer maturation, thus impacting several cellular functions, including biofilm formation, quorum sensing, and toxin synthesis [ 71 ]. For example, while cis-encoded antisense RNA of mucD (mucD_AS) regulates mucD expression and induces biofilm formation in Pseudomonas aeruginosa, micF as an asRNA in E. coli inhibits OmpF by destabilizing the mRNA and inhibiting translation [ 72 , 73 ].…”

Section: Discussionmentioning

confidence: 99%

Comparative transcriptomic analysis of Rickettsia conorii during in vitro infection of human and tick host cells

et al. 2020

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Background Pathogenic Rickettsia species belonging to the spotted fever group are arthropod-borne, obligate intracellular bacteria which exhibit preferential tropism for host microvascular endothelium in the mammalian hosts, resulting in disease manifestations attributed primarily to endothelial damage or dysfunction. Although rickettsiae are known to undergo evolution through genomic reduction, the mechanisms by which these pathogens regulate their transcriptome to ensure survival in tick vectors and maintenance by transovarial/transstadial transmission, in contrast to their ability to cause debilitating infections in human hosts remain unknown. In this study, we compare the expression profiles of rickettsial sRNAome/transcriptome and determine the transcriptional start sites (TSSs) of R. conorii transcripts during in vitro infection of human and tick host cells. Results We performed deep sequencing on total RNA from Amblyomma americanum AAE2 cells and human microvascular endothelial cells (HMECs) infected with R. conorii. Strand-specific RNA sequencing of R. conorii transcripts revealed the expression 32 small RNAs (Rc_sR’s), which were preferentially expressed above the limit of detection during tick cell infection, and confirmed the expression of Rc_sR61, sR71, and sR74 by quantitative RT-PCR. Intriguingly, a total of 305 and 132 R. conorii coding genes were differentially upregulated (> 2-fold) in AAE2 cells and HMECs, respectively. Further, enrichment for primary transcripts by treatment with Terminator 5′-Phosphate-dependent Exonuclease resulted in the identification of 3903 and 2555 transcription start sites (TSSs), including 214 and 181 primary TSSs in R. conorii during the infection to tick and human host cells, respectively. Seventy-five coding genes exhibited different TSSs depending on the host environment. Finally, we also observed differential expression of 6S RNA during host-pathogen and vector-pathogen interactions in vitro, implicating an important role for this noncoding RNA in the regulation of rickettsial transcriptome depending on the supportive host niche. Conclusions In sum, the findings of this study authenticate the presence of novel Rc_sR’s in R. conorii, reveal the first evidence for differential expression of coding transcripts and utilization of alternate transcriptional start sites depending on the host niche, and implicate a role for 6S RNA in the regulation of coding transcriptome during tripartite host-pathogen-vector interactions.

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Section: Discussionmentioning

confidence: 99%

Comparative transcriptomic analysis of Rickettsia conorii during in vitro infection of human and tick host cells

et al. 2020

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“…Since AAC(6′)-Ib is the major enzyme causing amikacin resistance in Gram-negative pathogens, it is expected that inhibition of its expression or activity would result in reversal of the resistant phenotype. Inhibition of expression of aac(6′)-Ib has been researched used antisense technologies, which are inspired by natural mechanisms of control of gene expression and DNA replication [ 236 , 237 , 238 , 239 , 240 ]. Several methodologies use different strategies to interfere with gene expression by supplying a short oligonucleotide or oligonucleotide analog that is complementary to a region of the target gene [ 241 , 242 , 243 , 244 , 245 , 246 ].…”

Section: Amikacinmentioning

confidence: 99%

Amikacin: Uses, Resistance, and Prospects for Inhibition

2017

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Aminoglycosides are a group of antibiotics used since the 1940s to primarily treat a broad spectrum of bacterial infections. The primary resistance mechanism against these antibiotics is enzymatic modification by aminoglycoside-modifying enzymes that are divided into acetyl-transferases, phosphotransferases, and nucleotidyltransferases. To overcome this problem, new semisynthetic aminoglycosides were developed in the 70s. The most widely used semisynthetic aminoglycoside is amikacin, which is refractory to most aminoglycoside modifying enzymes. Amikacin was synthesized by acylation with the l-(−)-γ-amino-α-hydroxybutyryl side chain at the C-1 amino group of the deoxystreptamine moiety of kanamycin A. The main amikacin resistance mechanism found in the clinics is acetylation by the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib], an enzyme coded for by a gene found in integrons, transposons, plasmids, and chromosomes of Gram-negative bacteria. Numerous efforts are focused on finding strategies to neutralize the action of AAC(6′)-Ib and extend the useful life of amikacin. Small molecules as well as complexes ionophore-Zn+2 or Cu+2 were found to inhibit the acetylation reaction and induced phenotypic conversion to susceptibility in bacteria harboring the aac(6′)-Ib gene. A new semisynthetic aminoglycoside, plazomicin, is in advance stage of development and will contribute to renewed interest in this kind of antibiotics.

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“…In addition to the many protein activators and repressors that control transcription initiation, there are also many non-coding RNAs (ncRNAs), including both small ncRNAs (sRNAs) and highly structured portions of mRNAs that play essential roles as regulatory elements controlling metabolism, stress-responses, and virulence [7–9]. Trans– acting small RNAs (sRNAs), which are found in intergenic regions [10] or derived from 3’ UTRs [11], allow selective degradation or translation of specific mRNAs [10]. Cis– acting mRNA structures, such as riboswitches, which interact with small molecules including metal ions, and protein ligands, and other regulatory sequences that are found in the long 3’ UTR of mRNAs, affect expression of their respective genes by regulating transcription attenuation or translation inhibition [12,13].…”

Section: Introductionmentioning

confidence: 99%

The Transcriptional landscape of Streptococcus pneumoniae TIGR4 reveals a complex operon architecture and abundant riboregulation critical for growth and virulence

et al. 2018

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Efficient and highly organized regulation of transcription is fundamental to an organism’s ability to survive, proliferate, and quickly respond to its environment. Therefore, precise mapping of transcriptional units and understanding their regulation is crucial to determining how pathogenic bacteria cause disease and how they may be inhibited. In this study, we map the transcriptional landscape of the bacterial pathogen Streptococcus pneumoniae TIGR4 by applying a combination of high-throughput RNA-sequencing techniques. We successfully map 1864 high confidence transcription termination sites (TTSs), 790 high confidence transcription start sites (TSSs) (742 primary, and 48 secondary), and 1360 low confidence TSSs (74 secondary and 1286 primary) to yield a total of 2150 TSSs. Furthermore, our study reveals a complex transcriptome wherein environment-respondent alternate transcriptional units are observed within operons stemming from internal TSSs and TTSs. Additionally, we identify many putative cis-regulatory RNA elements and riboswitches within 5’-untranslated regions (5’-UTR). By integrating TSSs and TTSs with independently collected RNA-Seq datasets from a variety of conditions, we establish the response of these regulators to changes in growth conditions and validate several of them. Furthermore, to demonstrate the importance of ribo-regulation by 5’-UTR elements for in vivo virulence, we show that the pyrR regulatory element is essential for survival, successful colonization and infection in mice suggesting that such RNA elements are potential drug targets. Importantly, we show that our approach of combining high-throughput sequencing with in vivo experiments can reconstruct a global understanding of regulation, but also pave the way for discovery of compounds that target (ribo-)regulators to mitigate virulence and antibiotic resistance.

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Natural antisense RNAs as mRNA regulatory elements in bacteria: a review on function and applications

Cited by 69 publications

References 75 publications

Comparative transcriptomic analysis of Rickettsia conorii during in vitro infection of human and tick host cells

Comparative transcriptomic analysis of Rickettsia conorii during in vitro infection of human and tick host cells

Amikacin: Uses, Resistance, and Prospects for Inhibition

The Transcriptional landscape of Streptococcus pneumoniae TIGR4 reveals a complex operon architecture and abundant riboregulation critical for growth and virulence

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