The Role of RNA Secondary Structure in Regulation of Gene Expression in Bacteria

Chełkowska-Pauszek, Agnieszka; Kosiński, Jan G.; Marciniak, Klementyna; Wysocka, Marta; Bąkowska-Żywicka, Kamilla; Żywicki, Marek

doi:10.3390/ijms22157845

Cited by 23 publications

(13 citation statements)

References 75 publications

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“…By contrast, PlzA has c‐di‐GMP‐independent RNA annealing activity, and we postulate that PlzA may act as a matchmaker chaperone aiding in sRNA and target RNA interactions throughout the enzootic cycle of the spirochete (Figure 7). We hypothesize that apo ‐PlzA may modulate RNA structure to regulate transcription, translation, and/or mRNA decay (Breaker, 2012; Chełkowska‐Pauszek et al, 2021; Kozak, 2005), but the details of the molecular mechanism(s) and role of PlzA‐RNA chaperone activity in gene regulation awaits further investigation.…”

Section: Resultsmentioning

confidence: 99%

c‐di‐GMP regulates activity of the PlzA RNA chaperone from the Lyme disease spirochete

Gundy

Patel

Bowler

et al. 2023

Molecular Microbiology

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PlzA is a c-di-GMP-binding protein crucial for adaptation of the Lyme disease spirochete Borrelia (Borreliella) burgdorferi during its enzootic life cycle. Unliganded apo-PlzA is important for vertebrate infection, while liganded holo-PlzA is important for survival in the tick; however, the biological function of PlzA has remained enigmatic.Here, we report that PlzA has RNA chaperone activity that is inhibited by c-di-GMP binding. Holo-and apo-PlzA bind RNA and accelerate RNA annealing, while only apo-PlzA can strand displace and unwind double-stranded RNA. Guided by the crystal structure of PlzA, we identified several key aromatic amino acids protruding from the N-and C-terminal domains that are required for RNA-binding and unwinding activity.Our findings illuminate c-di-GMP as a switch controlling the RNA chaperone activity of PlzA, and we propose that complex RNA-mediated modulatory mechanisms allow PlzA to regulate gene expression during both the vector and host phases of the B. burgdorferi life cycle.

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Section: Resultsmentioning

confidence: 99%

c‐di‐GMP regulates activity of the PlzA RNA chaperone from the Lyme disease spirochete

Gundy

Patel

Bowler

et al. 2023

Molecular Microbiology

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“…RNA secondary structure is especially important in defining an RNA molecule's roles and functions ( 65 , 66 ). These structures can be studied using a variety of techniques including secondary structure probing methods such as SHAPE, Nuclear Magnetic Resonance (NMR) spectroscopy, comparative sequence alignment and analysis, or three-dimensional structure predictions software for conceptualising higher order complexes ( 67–71 ).…”

Section: Discussionmentioning

confidence: 99%

Biophysical characterisation of human LincRNA-p21 sense and antisense Alu inverted repeats

D’Souza

Mrozowich

Badmalia

et al. 2022

Nucleic Acids Research

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Human Long Intergenic Noncoding RNA-p21 (LincRNA-p21) is a regulatory noncoding RNA that plays an important role in promoting apoptosis. LincRNA-p21 is also critical in down-regulating many p53 target genes through its interaction with a p53 repressive complex. The interaction between LincRNA-p21 and the repressive complex is likely dependent on the RNA tertiary structure. Previous studies have determined the two-dimensional secondary structures of the sense and antisense human LincRNA-p21 AluSx1 IRs using SHAPE. However, there were no insights into its three-dimensional structure. Therefore, we in vitro transcribed the sense and antisense regions of LincRNA-p21 AluSx1 Inverted Repeats (IRs) and performed analytical ultracentrifugation, size exclusion chromatography, light scattering, and small angle X-ray scattering (SAXS) studies. Based on these studies, we determined low-resolution, three-dimensional structures of sense and antisense LincRNA-p21. By adapting previously known two-dimensional information, we calculated their sense and antisense high-resolution models and determined that they agree with the low-resolution structures determined using SAXS. Thus, our integrated approach provides insights into the structure of LincRNA-p21 Alu IRs. Our study also offers a viable pipeline for combining the secondary structure information with biophysical and computational studies to obtain high-resolution atomistic models for long noncoding RNAs.

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“…35 RNAs from pathogens, including messenger RNA (mRNA), ribosomal RNA and viral RNA, always possess complex secondary structures such as double helical stems, and a selective TLR8 ligand, R2152, has a hairpin structure. 35,[47][48][49] RNase T2 and RNase 2 can also coordinately cleave these double-stranded RNA structures for TLR8 recognition. 35 Overall, the agonists of TLR8 have been summarized elsewhere.…”

Section: Ligands Recognized By Tlr8mentioning

confidence: 99%

A Biological Perspective of TLR8 Signaling in Host Defense and Inflammation

Bian

Dong

Wu³

et al. 2023

Infect Microb Dis

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Toll-like receptors (TLRs) play important roles in immune responses against pathogens and tumors. Recently, TLR8 has gained attention because of its association with multiple inflammatory diseases, infections and antitumor responses. TLR8 senses the degradation products of single-stranded RNA from microbes and self-released RNA to induce type I interferons, inflammatory gene expression and nucleotide-binding and oligomerization domain-, leucine-rich repeat-and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. So far, the understanding of TLR8 function in vivo is still limited, partially because of lacking a reliable rodent animal model. Murine Tlr8 cannot sense the ligands of human TLR8. In mammals, TLR8 distinguishes live bacteria from dead bacteria to regulate the magnitude of immune responses. Recently, TLR8 has been reported to recognize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA to induce inflammatory responses, suggesting that TLR8 participates in coronavirus disease 2019 . In this review, we discuss the mechanism of ligand recognition by TLR8, TLR8-mediated signaling pathways and signaling crosstalk between TLR8 and other molecules, and untangle the contribution of TLR8 to inflammatory diseases, infectious diseases, antitumor immunity and vaccination.

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The Role of RNA Secondary Structure in Regulation of Gene Expression in Bacteria

Cited by 23 publications

References 75 publications

c‐di‐GMP regulates activity of the PlzA RNA chaperone from the Lyme disease spirochete

c‐di‐GMP regulates activity of the PlzA RNA chaperone from the Lyme disease spirochete

Biophysical characterisation of human LincRNA-p21 sense and antisense Alu inverted repeats

A Biological Perspective of TLR8 Signaling in Host Defense and Inflammation

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