scholarly journals Computational prediction of nonenzymatic RNA degradation patterns

2017 ◽  
Vol 63 (4) ◽  
Author(s):  
Agnieszka Rybarczyk ◽  
Paulina Jackowiak ◽  
Marek Figlerowicz ◽  
Jacek Blazewicz
Keyword(s):  
Regulation Of Gene Expression ◽  
Computational Prediction ◽  
Rna Degradation ◽  
Branch And Cut ◽  
Structural Factors ◽  
Rna Molecules ◽  
Small Regulatory Rnas ◽  
Rna Fragments ◽  
Regulatory Rnas

Since the beginning of XXI century, the increasing interest in the research of ribonucleic acids has been observed in response to a surprising discovery of the role that RNA molecules play in the biological systems. It was demonstrated that they do not only take part in the protein synthesis (mRNA, rRNA, tRNA) but also are involved in the regulation of gene expression. Several classes of small regulatory RNAs have been discovered (e.g. microRNA, small interfering RNA, piwiRNA). Most of them are excised from specific double-stranded RNA precursors by enzymes that belong to the RNaseIII family (Drosha, Dicer or Dicer-like proteins). More recently, it has been shown that small regulatory RNAs are also generated as stable intermediates of RNA degradation (so called RNA fragments originating from tRNA, snRNA, snoRNA etc.). Unfortunately, the mechanisms underlying biogenesis of the RNA fragments remain unclear. It is thought that several factors may be involved in the formation of the RNA fragments. The most important are specific RNases, RNA-protein interactions and RNA structure.  In this work, we focus on RNA primary and secondary structures as factors influencing RNA stability and consequently the pattern of RNA fragmentation. Earlier, we identified major structural factors affecting non-enzymatic RNA degradation. Now based on these data we developed a new branch-and-cut algorithm that is able to predict the products of large RNA molecules hydrolysis in vitro. We also present the experimental data that verify the results generated using this algorithm.

scholarly journals Regulatory RNAs in Bacillus subtilis: a Gram-Positive Perspective on Bacterial RNA-Mediated Regulation of Gene Expression

2016 ◽  
Vol 80 (4) ◽  
pp. 1029-1057 ◽  
Author(s):  
Ruben A. T. Mars ◽  
Pierre Nicolas ◽  
Emma L. Denham ◽  
Jan Maarten van Dijl
Keyword(s):  
Gene Expression ◽  
Bacillus Subtilis ◽  
Regulation Of Gene Expression ◽  
Regulatory Rna ◽  
Gram Positive ◽  
Content Type ◽  
Rna Molecules ◽  
Small Regulatory Rnas ◽  
Regulatory Rnas ◽  
The Stability

SUMMARYBacteria can employ widely diverse RNA molecules to regulate their gene expression. Such molecules includetrans-acting small regulatory RNAs, antisense RNAs, and a variety of transcriptional attenuation mechanisms in the 5′ untranslated region. Thus far, most regulatory RNA research has focused on Gram-negative bacteria, such asEscherichia coliandSalmonella. Hence, there is uncertainty about whether the resulting insights can be extrapolated directly to other bacteria, such as the Gram-positive soil bacteriumBacillus subtilis. A recent study identified 1,583 putative regulatory RNAs inB. subtilis, whose expression was assessed across 104 conditions. Here, we review the current understanding of RNA-based regulation inB. subtilis, and we categorize the newly identified putative regulatory RNAs on the basis of their conservation in other bacilli and the stability of their predicted secondary structures. Our present evaluation of the publicly available data indicates that RNA-mediated gene regulation inB. subtilismostly involves elements at the 5′ ends of mRNA molecules. These can include 5′ secondary structure elements and metabolite-, tRNA-, or protein-binding sites. Importantly, sense-independent segments are identified as the most conserved and structured potential regulatory RNAs inB. subtilis. Altogether, the present survey provides many leads for the identification of new regulatory RNA functions inB. subtilis.

scholarly journals Insights into the Function of Regulatory RNAs in Bacteria and Archaea

2021 ◽  
Vol 1 (3) ◽  
pp. 403-423
Author(s):  
Elahe Soltani-Fard ◽  
Sina Taghvimi ◽  
Zahra Abedi Kichi ◽  
Christian Weber ◽  
Zahra Shabaninejad ◽  
...  
Keyword(s):  
Defense Mechanism ◽  
Regulation Of Gene Expression ◽  
Rna Molecules ◽  
Physiological Processes ◽  
Wide Range ◽  
Phage Dna ◽  
Small Molecule Ligands ◽  
Small Regulatory Rnas ◽  
Short Palindromic Repeat ◽  
Regulatory Rnas

Non-coding RNAs (ncRNAs) are functional RNA molecules that comprise about 80% of both mammals and prokaryotes genomes. Recent studies have identified a large number of small regulatory RNAs in Escherichia coli and other bacteria. In prokaryotes, RNA regulators are a diverse group of molecules that modulate a wide range of physiological responses through a variety of mechanisms. Similar to eukaryotes, bacterial microRNAs are an important class of ncRNAs that play an important role in the development and secretion of proteins and in the regulation of gene expression. Similarly, riboswitches are cis-regulatory structured RNA elements capable of directly controlling the expression of downstream genes in response to small molecule ligands. As a result, riboswitches detect and respond to the availability of various metabolic changes within cells. The most extensive and most widely studied set of small RNA regulators act through base pairing with RNAs. These types of RNAs are vital for prokaryotic life, activating or suppressing important physiological processes by modifying transcription or translation. The majority of these small RNAs control responses to changes in environmental conditions. Finally, clustered regularly interspaced short palindromic repeat (CRISPR) RNAs, a newly discovered RNA regulator group, contains short regions of homology to bacteriophage and plasmid sequences that bacteria use to splice phage DNA as a defense mechanism. The detailed mechanism is still unknown but devoted to target homologous foreign DNAs. Here, we review the known mechanisms and roles of non-coding regulatory RNAs, with particular attention to riboswitches and their functions, briefly introducing translational applications of CRISPR RNAs in mammals.

scholarly journals Stem-loops direct precise processing of 3′ UTR-derived small RNA MicL

2018 ◽  
Author(s):  
Taylor B Updegrove ◽  
Andrew B Kouse ◽  
Katarzyna J Bandyra ◽  
Gisela Storz
Keyword(s):  
Small Rna ◽  
Cleavage Site ◽  
Differential Sensitivity ◽  
Rnase E ◽  
Small Regulatory Rnas ◽  
Regulatory Rnas ◽  
Derivatives Of

AbstractIncreasing numbers of 3′UTR-derived small, regulatory RNAs (sRNAs) are being discovered in bacteria, most generated by cleavage from longer transcripts. The enzyme required for these cleavages has been reported to be RNase E, the major endoribonuclease in enterica bacteria. Previous studies investigating RNase E have come to a range of different conclusions regarding the determinants for RNase E processing. To understand the sequence and structure determinants for the precise processing of the 3′ UTR-derived sRNAs, we examined the cleavage of multiple mutant and chimeric derivatives of the 3′ UTR-derived MicL sRNA in vivo and in vitro. Our results revealed that tandem stem-loops 3′ to the cleavage site define optimal, correctly-positioned cleavage of MicL and likely other similar sRNAs. Moreover, our assays of MicL, ArcZ and CpxQ showed that sRNAs exhibit differential sensitivity to RNase E, likely a consequence of a hierarchy of sRNA features recognized by the endonuclease.

scholarly journals A novel computational approach for genome-wide prediction of small RNAs in bacteria

2014 ◽  
Author(s):  
Lei Li ◽  
Hoi Shan Kwan
Keyword(s):  
Small Rnas ◽  
Computational Prediction ◽  
Transcriptional Regulators ◽  
Structural Features ◽  
Extensive Study ◽  
Bacterial Physiology ◽  
Genome Wide ◽  
Small Regulatory Rnas ◽  
Regulatory Rnas ◽  
Window Approach

Small regulatory RNAs (sRNAs) are the most abundant post-transcriptional regulators in bacteria. They serve ubiquitous roles that control nearly every aspects of bacterial physiology. Identification of important features from sRNAs sequences will guide the computational prediction of new sRNA sequences for a better understanding of the pervasive sRNA-mediated regulation in bacteria. In this study, we have performed systematic analyses of many sequence and structural features that are possibly related to sRNA properties and identified a subset of significant features that effectively discriminate sRNAs sequences from random sequences. we then used a neural network model that integrated these subfeatures on unlabeled testing datasets, and it had achieved a 92.2% recall and 89.8% specificity. Finally, we applied this prediction model for genome-wide identification of sRNAs-encoded genes using a sliding-window approach. We recovered multiple known sRNAs and hundreds of predicted new sRNAs. These candidate novel sRNAs deserve extensive study to better understand the sRNA-mediated regulatory network in bacteria.

scholarly journals Small regulatory bacterial RNAs regulating the envelope stress response

2017 ◽  
Vol 45 (2) ◽  
pp. 417-425 ◽  
Author(s):  
Gracjana Klein ◽  
Satish Raina
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Degradation ◽  
Feedback Mechanism ◽  
Transcriptional Factors ◽  
Membrane Composition ◽  
Envelope Stress ◽  
Small Regulatory Rnas ◽  
Two Component Systems ◽  
Regulatory Rnas

Most bacteria encode a large repertoire of RNA-based regulatory mechanisms. Recent discoveries have revealed that the expression of many genes is controlled by a plethora of base-pairing noncoding small regulatory RNAs (sRNAs), regulatory RNA-binding proteins and RNA-degrading enzymes. Some of these RNA-based regulated processes respond to stress conditions and are involved in the maintenance of cellular homeostasis. They achieve it by either direct posttranscriptional repression of several mRNAs, including blocking access to ribosome and/or directing them to RNA degradation when the synthesis of their cognate proteins is unwanted, or by enhanced translation of some key stress-regulated transcriptional factors. Noncoding RNAs that regulate the gene expression by binding to regulatory proteins/transcriptional factors often act negatively by sequestration, preventing target recognition. Expression of many sRNAs is positively regulated by stress-responsive sigma factors like RpoE and RpoS, and two-component systems like PhoP/Q, Cpx and Rcs. Some of these regulatory RNAs act via a feedback mechanism on their own regulators, which is best reflected by recent discoveries, concerning the regulation of cell membrane composition by sRNAs in Escherichia coli and Salmonella, which are highlighted here.

scholarly journals The Etiological Agent of Lyme Disease, Borrelia burgdorferi, Appears To Contain Only a Few Small RNA Molecules

2004 ◽  
Vol 186 (24) ◽  
pp. 8472-8477 ◽  
Author(s):  
Yngve Östberg ◽  
Ignas Bunikis ◽  
Sven Bergström ◽  
Jörgen Johansson
Keyword(s):  
Borrelia Burgdorferi ◽  
Small Rna ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Rnase E ◽  
Regulatory Pathways ◽  
Rna Molecules ◽  
Small Regulatory Rnas ◽  
Regulatory Rnas

ABSTRACT Small regulatory RNAs (sRNAs) have recently been shown to be the main controllers of several regulatory pathways. The function of sRNAs depends in many cases on the RNA-binding protein Hfq, especially for sRNAs with an antisense function. In this study, the genome of Borrelia burgdorferi was subjected to different searches for sRNAs, including direct homology and comparative genomics searches and ortholog- and annotation-based search strategies. Two new sRNAs were found, one of which showed complementarity to the rpoS region, which it possibly controls by an antisense mechanism. The role of the other sRNA is unknown, although observed complementarities against particular mRNA sequences suggest an antisense mechanism. We suggest that the low level of sRNAs observed in B. burgdorferi is at least partly due to the presumed lack of both functional Hfq protein and RNase E activity.

scholarly journals Polynucleotide Phosphorylase Functions as Both an Exonuclease and a Poly(A) Polymerase in Spinach Chloroplasts

2001 ◽  
Vol 21 (16) ◽  
pp. 5408-5416 ◽  
Author(s):  
Shlomit Yehudai-Resheff ◽  
Merav Hirsh ◽  
Gadi Schuster
Keyword(s):  
Transit Peptide ◽  
Rna Degradation ◽  
Polynucleotide Phosphorylase ◽  
Chloroplast Transit Peptide ◽  
Stem Loop ◽  
Rna Molecules ◽  
Spinach Chloroplasts ◽  
Endonucleolytic Cleavage ◽  
Exonucleolytic Degradation

ABSTRACT The molecular mechanism of mRNA degradation in the chloroplast consists of sequential events including endonucleolytic cleavage, the addition of poly(A)-rich sequences to the endonucleolytic cleavage products, and exonucleolytic degradation by polynucleotide phosphorylase (PNPase). In Escherichia coli,polyadenylation is performed mainly by poly(A)-polymerase (PAP) I or by PNPase in its absence. While trying to purify the chloroplast PAP by following in vitro polyadenylation activity, it was found to copurify with PNPase and indeed could not be separated from it. Purified PNPase was able to polyadenylate RNA molecules with an activity similar to that of lysed chloroplasts. Both activities use ADP much more effectively than ATP and are inhibited by stem-loop structures. The activity of PNPase was directed to RNA degradation or polymerization by manipulating physiologically relevant concentrations of Piand ADP. As expected of a phosphorylase, Pi enhanced degradation, whereas ADP inhibited degradation and enhanced polymerization. In addition, searching the completeArabidopsis genome revealed several putative PAPs, none of which were preceded by a typical chloroplast transit peptide. These results suggest that there is no enzyme similar to E. coli PAP I in spinach chloroplasts and that polyadenylation and exonucleolytic degradation of RNA in spinach chloroplasts are performed by one enzyme, PNPase.

scholarly journals Co-surveillance of ribosomal RNA by the exosome complex and nucleolar RNAi in C. elegans

2020 ◽  
Author(s):  
Shimiao Liao ◽  
Xiangyang Chen ◽  
Ting Xu ◽  
Qile Jin ◽  
Zongxiu Xu ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Degradation ◽  
Rna Polymerase I ◽  
C Elegans ◽  
Small Regulatory Rnas ◽  
Regulatory Rnas ◽  
Rna Exosome ◽  
Polymerase I ◽  
Nuclear Rnai ◽  
Novel Model

AbstractEukaryotic cells express a wide variety of endogenous small regulatory RNAs that function in the nucleus. We previously found that erroneous rRNAs induce the generation of antisense ribosomal siRNAs (risiRNAs) which silence the expression of rRNAs via the nuclear RNAi defective (Nrde) pathway. To further understand the biological roles and mechanisms of this class of small regulatory RNAs, we conducted forward genetic screening to identify factors involved in risiRNA generation in Caenorhabditis elegans. We found that risiRNAs accumulated in the RNA exosome mutants. risiRNAs directed a NRDE-dependent silencing of pre-rRNAs in the nucleolus. In the presence of risiRNA, NRDE-2 accumulated in the nucleolus and colocalized with RNA polymerase I. risiRNA inhibited the transcription elongation of RNA polymerase I by decreasing RNAP I occupancy downstream of the site of RNAi. Meanwhile, exosome mislocalized from the nucleolus to nucleoplasm in suppressor of siRNA (susi) mutants, in which erroneous rRNAs accumulated. These results establish a novel model of rRNA surveillance by combining ribonuclease-mediated RNA degradation with small RNA-directed nucleolar RNAi system.

scholarly journals Neisseria meningitidis Uses Sibling Small Regulatory RNAs To Switch from Cataplerotic to Anaplerotic Metabolism

mBio ◽  
2017 ◽  
Vol 8 (2) ◽  
Author(s):  
Yvonne Pannekoek ◽  
Robert A. G. Huis in ‘t Veld ◽  
Kim Schipper ◽  
Sandra Bovenkerk ◽  
Gertjan Kramer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neisseria Meningitidis ◽  
Tricarboxylic Acid Cycle ◽  
Regulation Of Gene Expression ◽  
Stringent Response ◽  
Tricarboxylic Acid ◽  
Metabolic Adaptation ◽  
Acid Cycle ◽  
Small Regulatory Rnas ◽  
Regulatory Rnas

ABSTRACT Neisseria meningitidis (the meningococcus) is primarily a commensal of the human oropharynx that sporadically causes septicemia and meningitis. Meningococci adapt to diverse local host conditions differing in nutrient supply, like the nasopharynx, blood, and cerebrospinal fluid, by changing metabolism and protein repertoire. However, regulatory transcription factors and two-component systems in meningococci involved in adaptation to local nutrient variations are limited. We identified novel sibling small regulatory RNAs ( Neisseria metabolic switch regulators [NmsRs]) regulating switches between cataplerotic and anaplerotic metabolism in this pathogen. Overexpression of NmsRs was tolerated in blood but not in cerebrospinal fluid. Expression of six tricarboxylic acid cycle enzymes was downregulated by direct action of NmsRs. Expression of the NmsRs themselves was under the control of the stringent response through the action of RelA. Small sibling regulatory RNAs of meningococci, controlling general metabolic switches, add an exciting twist to their versatile repertoire in bacterial pathogens. IMPORTANCE Regulatory small RNAs (sRNAs) of pathogens are coming to be recognized as highly important components of riboregulatory networks, involved in the control of essential cellular processes. They play a prominent role in adaptation to physiological changes as represented by different host environments. They can function as posttranscriptional regulators of gene expression to orchestrate metabolic adaptation to nutrient stresses. Here, we identified highly conserved sibling sRNAs in Neisseria meningitidis which are functionally involved in the regulation of gene expression of components of the tricarboxylic acid cycle. These novel sibling sRNAs that function by antisense mechanisms extend the so-called stringent response which connects metabolic status to colonization and possibly virulence as well as pathogenesis in meningococci. IMPORTANCE Regulatory small RNAs (sRNAs) of pathogens are coming to be recognized as highly important components of riboregulatory networks, involved in the control of essential cellular processes. They play a prominent role in adaptation to physiological changes as represented by different host environments. They can function as posttranscriptional regulators of gene expression to orchestrate metabolic adaptation to nutrient stresses. Here, we identified highly conserved sibling sRNAs in Neisseria meningitidis which are functionally involved in the regulation of gene expression of components of the tricarboxylic acid cycle. These novel sibling sRNAs that function by antisense mechanisms extend the so-called stringent response which connects metabolic status to colonization and possibly virulence as well as pathogenesis in meningococci.

scholarly journals Conservation of Small Regulatory RNAs in Vibrio parahaemolyticus: Possible role of RNA-OUT Encoded by the Pathogenicity Island (VPaI-7) of Pandemic Strains

2019 ◽  
Vol 20 (11) ◽  
pp. 2827
Author(s):  
Nicolás Plaza ◽  
Diliana Pérez-Reytor ◽  
Sebastián Ramírez-Araya ◽  
Alequis Pavón ◽  
Gino Corsini ◽  
...  
Keyword(s):  
Vibrio Parahaemolyticus ◽  
Regulation Of Gene Expression ◽  
Pathogenicity Island ◽  
Vibrio Species ◽  
Transcriptional Level ◽  
Adverse Conditions ◽  
Small Regulatory Rnas ◽  
Regulatory Rnas ◽  
Pandemic Strains

Small regulatory RNAs (sRNAs) are molecules that play an important role in the regulation of gene expression. sRNAs in bacteria can affect important processes, such as metabolism and virulence. Previous studies showed a significant role of sRNAs in the Vibrio species, but knowledge about Vibrio parahaemolyticus is limited. Here, we examined the conservation of sRNAs between V. parahaemolyticus and other human Vibrio species, in addition to investigating the conservation between V. parahaemolyticus strains differing in pandemic origin. Our results showed that only 7% of sRNAs were conserved between V. parahaemolyticus and other species, but 88% of sRNAs were highly conserved within species. Nonetheless, two sRNAs coding to RNA-OUT, a component of the Tn10/IS10 system, were exclusively present in pandemic strains. Subsequent analysis showed that both RNA-OUT were located in pathogenicity island-7 and would interact with transposase VPA1379, according to the model of pairing of IS10-encoded antisense RNAs. According to the location of RNA-OUT/VPA1379, we also investigated if they were expressed during infection. We observed that the transcriptional level of VPA1379 was significantly increased, while RNA-OUT was decreased at three hours post-infection. We suggest that IS10 transcription increases in pandemic strains during infection, probably to favor IS10 transposition and improve their fitness when they are facing adverse conditions.

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