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 Neurogenesis: Regulation by Alternative Splicing and Related Posttranscriptional Processes

2016 ◽  
Vol 23 (5) ◽  
pp. 466-477 ◽  
Author(s):  
Enrique Lara-Pezzi ◽  
Manuel Desco ◽  
Alberto Gatto ◽  
María Victoria Gómez-Gaviro
Keyword(s):  
Alternative Splicing ◽  
Protein Function ◽  
Posttranscriptional Regulation ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Degradation ◽  
Protein Isoforms ◽  
Mammalian Brain ◽  
Nonsense Mediated Decay

The complexity of the mammalian brain requires highly specialized protein function and diversity. As neurons differentiate and the neuronal circuitry is established, several mRNAs undergo alternative splicing and other posttranscriptional changes that expand the variety of protein isoforms produced. Recent advances are beginning to shed light on the molecular mechanisms that regulate isoform switching during neurogenesis and the role played by specific RNA binding proteins in this process. Neurogenesis and neuronal wiring were recently shown to also be regulated by RNA degradation through nonsense-mediated decay. An additional layer of regulatory complexity in these biological processes is the interplay between alternative splicing and long noncoding RNAs. Dysregulation of posttranscriptional regulation results in defective neuronal differentiation and/or synaptic connections that lead to neurodevelopmental and psychiatric disorders.

scholarly journals Multiple in vivo roles for the C-terminal domain of the RNA chaperone Hfq

2021 ◽  
Author(s):  
Kumari Kavita ◽  
Aixia Zhang ◽  
Chin-Hsien Tai ◽  
Nadim Majdalani ◽  
Gisela Storz ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Rna Binding ◽  
Class Ii ◽  
Rna Chaperone ◽  
Terminal Domain ◽  
C Terminus ◽  
Bacterial Rna ◽  
Small Regulatory Rnas ◽  
Regulatory Rnas

Hfq, a bacterial RNA chaperone, stabilizes small regulatory RNAs (sRNAs) and facilitates sRNA base-pairing with target mRNAs. Hfq has a conserved N-terminal domain and a poorly conserved disordered C-terminal domain (CTD). In a transcriptome-wide examination of the effects of a chromosomal CTD deletion (Hfq1-65), the Escherichia coli mutant was most defective for the accumulation of sRNAs that bind the proximal and distal faces of Hfq (Class II sRNAs), but other sRNAs also were affected. There were only modest effects on the levels of mRNAs, suggesting little disruption of sRNA-dependent regulation. However, cells expressing Hfq lacking the CTD deletion in combination with a weak distal face mutation were defective for the function of the Class II sRNA ChiX and repression of mutS, both dependent upon distal face RNA binding. Loss of the region between amino acids 66-72 was critical for this defect. The CTD region beyond amino acid 72 was not necessary for distal face-dependent regulation, but was needed for functions associated with the Hfq rim, seen most clearly in combination with a rim mutant. Our results suggest that the C-terminus collaborates in various ways with different binding faces of Hfq, leading to distinct outcomes for individual sRNAs.

scholarly journals Conceptual Advances in Control of Inflammation by the RNA-Binding Protein Tristetraprolin

2021 ◽  
Vol 12 ◽  
Author(s):  
Pavel Kovarik ◽  
Annika Bestehorn ◽  
Jeanne Fesselet
Keyword(s):  
Immune Responses ◽  
Mrna Stability ◽  
Binding Sites ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Degradation ◽  
Decay Rates ◽  
Mrna Destabilization

Regulated changes in mRNA stability are critical drivers of gene expression adaptations to immunological cues. mRNA stability is controlled mainly by RNA-binding proteins (RBPs) which can directly cleave mRNA but more often act as adaptors for the recruitment of the RNA-degradation machinery. One of the most prominent RBPs with regulatory roles in the immune system is tristetraprolin (TTP). TTP targets mainly inflammation-associated mRNAs for degradation and is indispensable for the resolution of inflammation as well as the maintenance of immune homeostasis. Recent advances in the transcriptome-wide knowledge of mRNA expression and decay rates together with TTP binding sites in the target mRNAs revealed important limitations in our understanding of molecular mechanisms of TTP action. Such orthogonal analyses lead to the discovery that TTP binding destabilizes some bound mRNAs but not others in the same cell. Moreover, comparisons of various immune cells indicated that an mRNA can be destabilized by TTP in one cell type while it remains stable in a different cell linage despite the presence of TTP. The action of TTP extends from mRNA destabilization to inhibition of translation in a subset of targets. This article will discuss these unexpected context-dependent functions and their implications for the regulation of immune responses. Attention will be also payed to new insights into the role of TTP in physiology and tissue homeostasis.

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 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 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 N6-methyladenosine dynamics during early vertebrate embryogenesis

2019 ◽  
Author(s):  
Håvard Aanes ◽  
Dominique Engelsen ◽  
Adeel Manaf ◽  
Endalkachew Ashenafi Alemu ◽  
Cathrine Broberg Vågbø ◽  
...  
Keyword(s):  
Translational Regulation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Degradation ◽  
Translational Efficiency ◽  
Mrna Levels ◽  
Maternal Transcripts ◽  
Post Transcriptional Regulation ◽  
Genome Activation ◽  
Polyadenylated Mrna

AbstractEarly vertebrate embryogenesis is characterized by extensive post-transcriptional regulation during the maternal-to-zygotic transition. The N6-methyladenosine (m6A) modifications on mRNA have been shown to affect both translation and stability of transcripts. Here we investigate the m6A topology during early vertebrate embryogenesis and its association with polyadenylated mRNA levels. The majority (>70%) of maternal transcripts harbor m6A, and there is a substantial increase of m6A in the polyadenylated mRNA fraction between 0 and 2 hours post fertilization. Notably, we find strong associations between m6A, cytoplasmic polyadenylation and translational efficiency prior to zygotic genome activation (ZGA). Interestingly, the relationship between m6A and translation is strongest for peaks located in the 3’UTR, but not overlapping stop codons. Sequence analyses revealed enrichment of motifs for RNA binding proteins involved in translational regulation and RNA degradation. After ZGA, m6A seem to diminish the effect of miR-430 mediated degradation. The reported results improve our understanding of the combinatorial code behind post-transcriptional mRNA regulation during embryonic reprogramming and early differentiation.

scholarly journals Changes in mRNA abundance drive shuttling of RNA binding proteins, linking cytoplasmic RNA degradation to transcription

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Sarah Gilbertson ◽  
Joel D Federspiel ◽  
Ella Hartenian ◽  
Ileana M Cristea ◽  
Britt Glaunsinger
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Mrna Decay ◽  
Binding Proteins ◽  
Rna Binding ◽  
Nuclear Translocation ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Protein Localization ◽  
Rna Degradation

Alterations in global mRNA decay broadly impact multiple stages of gene expression, although signals that connect these processes are incompletely defined. Here, we used tandem mass tag labeling coupled with mass spectrometry to reveal that changing the mRNA decay landscape, as frequently occurs during viral infection, results in subcellular redistribution of RNA binding proteins (RBPs) in human cells. Accelerating Xrn1-dependent mRNA decay through expression of a gammaherpesviral endonuclease drove nuclear translocation of many RBPs, including poly(A) tail-associated proteins. Conversely, cells lacking Xrn1 exhibited changes in the localization or abundance of numerous factors linked to mRNA turnover. Using these data, we uncovered a new role for relocalized cytoplasmic poly(A) binding protein in repressing recruitment of TATA binding protein and RNA polymerase II to promoters. Collectively, our results show that changes in cytoplasmic mRNA decay can directly impact protein localization, providing a mechanism to connect seemingly distal stages of gene expression.

scholarly journals System-wide analyses of the fission yeast poly(A)+ RNA interactome reveal insights into organisation and function of RNA-protein complexes

2019 ◽  
Author(s):  
Cornelia Kilchert ◽  
Tea Kecman ◽  
Emily Priest ◽  
Svenja Hester ◽  
Krzysztof Kus ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Protein Interactions ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Protein Complexes ◽  
Rna Degradation ◽  
Binding Activity ◽  
Rna Exosome ◽  
And Function ◽  
Rna Protein Complexes

AbstractProduction, function, and turnover of mRNA are orchestrated by multi-subunit machineries that play a central role in gene expression. Within these molecular machines, interactions with the target mRNA are mediated by RNA-binding proteins (RBPs), and the accuracy and dynamics of these RNA-protein interactions are essential for their function. Here, we show that fission yeast whole cell poly(A)+ RNA-protein crosslinking data provides system-wide information on the organisation and function of the RNA-protein complexes. We evaluate relative enrichment of cellular RBPs on poly(A)+ RNA to identify interactors with high RNA-binding activity and provide key information about the RNA-binding properties of large multi-protein complexes, such as the mRNA 3’ end processing machinery (cleavage and polyadenylation factor, CPF) and the RNA exosome. We demonstrate that different functional modules within CPF differ in their ability to interact with RNA. Importantly, we reveal that CPF forms additional contacts with RNA via the Fip1 subunit of the polyadenylation module and two subunits of the nuclease module. In addition, our data highlights the central role of the RNA helicase Mtl1 in RNA degradation by the exosome as mutations in Mtl1 lead to disengagement of the exosome from RNA. We examine how routes of substrate access to the complex are affected upon mutation of exosome subunits. Our results provide important insights into how different components of the exosome contribute to engagement of the complex with substrate RNA. Overall, our data uncover how multi-subunit cellular machineries interact with RNA, on a proteome-wide scale.

scholarly journals An Inventory of CiaR-Dependent Small Regulatory RNAs in Streptococci

2021 ◽  
Vol 12 ◽  
Author(s):  
Nancy Jabbour ◽  
Marie-Frédérique Lartigue
Keyword(s):  
Farm Animals ◽  
Bacterial Survival ◽  
Rna Translation ◽  
Component Systems ◽  
Small Regulatory Rnas ◽  
Streptococcal Species ◽  
Two Component Systems ◽  
Regulatory Rnas ◽  
Physical And Chemical

Bacteria adapt to the different environments encountered by rapid and tightly controlled regulations involving complex networks. A first line of control is transcriptional with regulators such as two-component systems (TCSs) that respond to physical and chemical perturbations. It is followed by posttranscriptional regulations in which small regulatory RNAs (sRNAs) may affect RNA translation. Streptococci are opportunistic pathogens for humans and farm animals. The TCS CiaRH is highly conserved among this genus and crucial in bacterial survival under stressful conditions. In several streptococcal species, some sRNAs belong to the CiaRH regulon and are called csRNAs for cia-dependent sRNAs. In this review, we start by focusing on the Streptococcus species harboring a CiaRH TCS. Then the role of CiaRH in streptococcal pathogenesis is discussed in the context of recent studies. Finally, we give an overview of csRNAs and their functions in Streptococci with a focus on their importance in bacterial adaptation and virulence.

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