Small RNAs Participate in Plant–Virus Interaction and Their Application in Plant Viral Defense

Small RNAs are significant regulators of gene expression, which play multiple roles in plant development, growth, reproductive and stress response. It is generally believed that the regulation of plants’ endogenous genes by small RNAs has evolved from a cellular defense mechanism for RNA viruses and transposons. Most small RNAs have well-established roles in the defense response, such as viral response. During viral infection, plant endogenous small RNAs can direct virus resistance by regulating the gene expression in the host defense pathway, while the small RNAs derived from viruses are the core of the conserved and effective RNAi resistance mechanism. As a counter strategy, viruses evolve suppressors of the RNAi pathway to disrupt host plant silencing against viruses. Currently, several studies have been published elucidating the mechanisms by which small RNAs regulate viral defense in different crops. This paper reviews the distinct pathways of small RNAs biogenesis and the molecular mechanisms of small RNAs mediating antiviral immunity in plants, as well as summarizes the coping strategies used by viruses to override this immune response. Finally, we discuss the current development state of the new applications in virus defense based on small RNA silencing.

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Network Analyses Predict Small RNAs That Might Modulate Gene Expression in the Testis and Epididymis of Bos indicus Bulls

Frontiers in Genetics ◽

10.3389/fgene.2021.610116 ◽

2021 ◽

Vol 12 ◽

Author(s):

Andressa O. de Lima ◽

Juliana Afonso ◽

Janette Edson ◽

Esteban Marcellin ◽

Robin Palfreyman ◽

...

Keyword(s):

Gene Expression ◽

Small Rnas ◽

Molecular Mechanisms ◽

Bos Indicus ◽

Male Gamete ◽

Functional Enrichment ◽

Pairwise Comparisons ◽

Network Analyses ◽

Germ Cell Differentiation ◽

Network Cluster

Spermatogenesis relies on complex molecular mechanisms, essential for the genesis and differentiation of the male gamete. Germ cell differentiation starts at the testicular parenchyma and finishes in the epididymis, which has three main regions: head, body, and tail. RNA-sequencing data of the testicular parenchyma (TP), head epididymis (HE), and tail epididymis (TE) from four bulls (three biopsies per bull: 12 samples) were subjected to differential expression analyses, functional enrichment analyses, and co-expression analyses. The aim was to investigate the co-expression and infer possible regulatory roles for transcripts involved in the spermatogenesis of Bos indicus bulls. Across the three pairwise comparisons, 3,826 differentially expressed (DE) transcripts were identified, of which 384 are small RNAs. Functional enrichment analysis pointed to gene ontology (GO) terms related to ion channel activity, detoxification of copper, neuroactive receptors, and spermatogenesis. Using the regulatory impact factor (RIF) algorithm, we detected 70 DE small RNAs likely to regulate the DE transcripts considering all pairwise comparisons among tissues. The pattern of small RNA co-expression suggested that these elements are involved in spermatogenesis regulation. The 3,826 DE transcripts (mRNAs and small RNAs) were further subjected to co-expression analyses using the partial correlation and information theory (PCIT) algorithm for network prediction. Significant correlations underpinned the co-expression network, which had 2,216 transcripts connected by 158,807 predicted interactions. The larger network cluster was enriched for male gamete generation and had 15 miRNAs with significant RIF. The miRNA bta-mir-2886 showed the highest number of connections (601) and was predicted to down-regulate ELOVL3, FEZF2, and HOXA13 (negative co-expression correlations and confirmed with TargetScan). In short, we suggest that bta-mir-2886 and other small RNAs might modulate gene expression in the testis and epididymis, in Bos indicus cattle.

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Widespread roles for piRNAs and WAGO-class siRNAs in shaping the germline transcriptome of Caenorhabditis elegans

Nucleic Acids Research ◽

10.1093/nar/gkz1178 ◽

2019 ◽

Vol 48 (4) ◽

pp. 1811-1827 ◽

Cited By ~ 11

Author(s):

Kailee J Reed ◽

Joshua M Svendsen ◽

Kristen C Brown ◽

Brooke E Montgomery ◽

Taylor N Marks ◽

...

Keyword(s):

Gene Expression ◽

Caenorhabditis Elegans ◽

Small Rnas ◽

High Throughput Sequencing ◽

Critical Role ◽

Rnai Pathway ◽

Small Interfering Rnas ◽

Germline Development ◽

Histone Mrnas ◽

High Level

Abstract Piwi-interacting RNAs (piRNAs) and small interfering RNAs (siRNAs) are distinct classes of small RNAs required for proper germline development. To identify the roles of piRNAs and siRNAs in regulating gene expression in Caenorhabditis elegans, we subjected small RNAs and mRNAs from the gonads of piRNA and siRNA defective mutants to high-throughput sequencing. We show that piRNAs and an abundant class of siRNAs known as WAGO-class 22G-RNAs are required for proper expression of spermatogenic and oogenic genes. WAGO-class 22G-RNAs are also broadly required for transposon silencing, whereas piRNAs are largely dispensable. piRNAs, however, have a critical role in controlling histone gene expression. In the absence of piRNAs, histone mRNAs are misrouted into the nuclear RNAi pathway involving the Argonaute HRDE-1, concurrent with a reduction in the expression of many histone mRNAs. We also show that high-level gene expression in the germline is correlated with high level 22G-RNA production. However, most highly expressed genes produce 22G-RNAs through a distinct pathway that presumably involves the Argonaute CSR-1. In contrast, genes targeted by the WAGO branch of the 22G-RNA pathway are typically poorly expressed and respond unpredictably to loss of 22G-RNAs. Our results point to broad roles for piRNAs and siRNAs in controlling gene expression in the C. elegans germline.

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Comparative transcriptomics reveals a conserved Bacterial Adaptive Phage Response (BAPR) to viral predation

10.1101/248849 ◽

2018 ◽

Cited By ~ 11

Author(s):

Bob G. Blasdel ◽

Pieter-Jan Ceyssens ◽

Anne Chevallereau ◽

Laurent Debarbieux ◽

Rob Lavigne

Keyword(s):

Molecular Mechanisms ◽

Defense Mechanism ◽

Resistance Mechanism ◽

Comparative Transcriptomics ◽

Adaptive Resistance ◽

Pseudomonas Quinolone Signal ◽

Host Defense Mechanism ◽

Infected Cells ◽

Adaptive Stress Response ◽

Restriction Modification

AbstractIntrinsic and acquired defenses against bacteriophages, including Restriction/Modification, CRISPR/Cas, and Toxin/Anti-toxin systems have been intensely studied, with profound scientific impacts. However, adaptive defenses against phage infection analogous to adaptive resistance to antimicrobials have yet to be described. To identify such mechanisms, we applied an RNAseq-based, comparative transcriptomics approach in differentPseudomonas aeruginosastrains after independent infection by a set of divergent virulent bacteriophages. A common host-mediated adaptive stress response to phages was identified that includes the Pseudomonas Quinolone Signal, through which infected cells inform their neighbors of infection, and what may be a resistance mechanism that functions by reducing infection vigor. With host transcriptional machinery left intact, we also observe phage-mediated differential expression caused by phage-specific stresses and molecular mechanisms. These responses suggest the presence of a conserved Bacterial Adaptive Phage Response mechanism as a novel type of host defense mechanism, and which may explain transient forms of phage persistence.

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The Mechanisms Behind the Biological Activity of Flavonoids

Current Medicinal Chemistry ◽

10.2174/0929867325666180706104829 ◽

2019 ◽

Vol 26 (39) ◽

pp. 6976-6990 ◽

Cited By ~ 12

Author(s):

Ana María González-Paramás ◽

Begoña Ayuda-Durán ◽

Sofía Martínez ◽

Susana González-Manzano ◽

Celestino Santos-Buelga

Keyword(s):

Gene Expression ◽

Biological Activity ◽

Phenolic Compounds ◽

Intracellular Signaling ◽

Molecular Mechanisms ◽

Radical Scavenging ◽

Model Organism ◽

Stress Theory ◽

Radical Scavenging Properties

: Flavonoids are phenolic compounds widely distributed in the human diet. Their intake has been associated with a decreased risk of different diseases such as cancer, immune dysfunction or coronary heart disease. However, the knowledge about the mechanisms behind their in vivo activity is limited and still under discussion. For years, their bioactivity was associated with the direct antioxidant and radical scavenging properties of phenolic compounds, but nowadays this assumption is unlikely to explain their putative health effects, or at least to be the only explanation for them. New hypotheses about possible mechanisms have been postulated, including the influence of the interaction of polyphenols and gut microbiota and also the possibility that flavonoids or their metabolites could modify gene expression or act as potential modulators of intracellular signaling cascades. This paper reviews all these topics, from the classical view as antioxidants in the context of the Oxidative Stress theory to the most recent tendencies related with the modulation of redox signaling pathways, modification of gene expression or interactions with the intestinal microbiota. The use of C. elegans as a model organism for the study of the molecular mechanisms involved in biological activity of flavonoids is also discussed.

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The Integrated RNA Landscape of Renal Preconditioning against Ischemia-Reperfusion Injury

Journal of the American Society of Nephrology ◽

10.1681/asn.2019050534 ◽

2020 ◽

Vol 31 (4) ◽

pp. 716-730 ◽

Cited By ~ 1

Author(s):

Marc Johnsen ◽

Torsten Kubacki ◽

Assa Yeroslaviz ◽

Martin Richard Späth ◽

Jannis Mörsdorf ◽

...

Keyword(s):

Gene Expression ◽

Reperfusion Injury ◽

Caloric Restriction ◽

Molecular Mechanisms ◽

Target Genes ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Hypoxic Preconditioning ◽

Preventive Strategies ◽

Gene Expression Signatures

BackgroundAlthough AKI lacks effective therapeutic approaches, preventive strategies using preconditioning protocols, including caloric restriction and hypoxic preconditioning, have been shown to prevent injury in animal models. A better understanding of the molecular mechanisms that underlie the enhanced resistance to AKI conferred by such approaches is needed to facilitate clinical use. We hypothesized that these preconditioning strategies use similar pathways to augment cellular stress resistance.MethodsTo identify genes and pathways shared by caloric restriction and hypoxic preconditioning, we used RNA-sequencing transcriptome profiling to compare the transcriptional response with both modes of preconditioning in mice before and after renal ischemia-reperfusion injury.ResultsThe gene expression signatures induced by both preconditioning strategies involve distinct common genes and pathways that overlap significantly with the transcriptional changes observed after ischemia-reperfusion injury. These changes primarily affect oxidation-reduction processes and have a major effect on mitochondrial processes. We found that 16 of the genes differentially regulated by both modes of preconditioning were strongly correlated with clinical outcome; most of these genes had not previously been directly linked to AKI.ConclusionsThis comparative analysis of the gene expression signatures in preconditioning strategies shows overlapping patterns in caloric restriction and hypoxic preconditioning, pointing toward common molecular mechanisms. Our analysis identified a limited set of target genes not previously known to be associated with AKI; further study of their potential to provide the basis for novel preventive strategies is warranted. To allow for optimal interactive usability of the data by the kidney research community, we provide an online interface for user-defined interrogation of the gene expression datasets (http://shiny.cecad.uni-koeln.de:3838/IRaP/).

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Modulation of the Immune Response by Deferasirox in Myelodysplastic Syndrome Patients

Pharmaceuticals ◽

10.3390/ph14010041 ◽

2021 ◽

Vol 14 (1) ◽

pp. 41

Author(s):

Hana Votavova ◽

Zuzana Urbanova ◽

David Kundrat ◽

Michaela Dostalova Merkerova ◽

Martin Vostry ◽

...

Keyword(s):

Gene Expression ◽

Immune Response ◽

Blood Cell ◽

Myelodysplastic Syndrome ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Adaptive Immune Response ◽

Gene Expression Profiles ◽

Iron Chelator ◽

Multiple Cancer

Deferasirox (DFX) is an oral iron chelator used to reduce iron overload (IO) caused by frequent blood cell transfusions in anemic myelodysplastic syndrome (MDS) patients. To study the molecular mechanisms by which DFX improves outcome in MDS, we analyzed the global gene expression in untreated MDS patients and those who were given DFX treatment. The gene expression profiles of bone marrow CD34+ cells were assessed by whole-genome microarrays. Initially, differentially expressed genes (DEGs) were determined between patients with normal ferritin levels and those with IO to address the effect of excessive iron on cellular pathways. These DEGs were annotated to Gene Ontology terms associated with cell cycle, apoptosis, adaptive immune response and protein folding and were enriched in cancer-related pathways. The deregulation of multiple cancer pathways in iron-overloaded patients suggests that IO is a cofactor favoring the progression of MDS. The DEGs between patients with IO and those treated with DFX were involved predominantly in biological processes related to the immune response and inflammation. These data indicate DFX modulates the immune response mainly via neutrophil-related genes. Suppression of negative regulators of blood cell differentiation essential for cell maturation and upregulation of heme metabolism observed in DFX-treated patients may contribute to the hematopoietic improvement.

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Mapping chromatin accessibility and active regulatory elements reveals pathological mechanisms in human gliomas

Nature Communications ◽

10.1038/s41467-021-23922-2 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Karolina Stępniak ◽

Magdalena A. Machnicka ◽

Jakub Mieczkowski ◽

Anna Macioszek ◽

Bartosz Wojtaś ◽

...

Keyword(s):

Gene Expression ◽

Chromatin Structure ◽

Molecular Mechanisms ◽

Genome Mapping ◽

Malignant Gliomas ◽

Regulatory Elements ◽

Chromatin Accessibility ◽

Multiple Tumor ◽

Genes Encoding ◽

Methylation Patterns

AbstractChromatin structure and accessibility, and combinatorial binding of transcription factors to regulatory elements in genomic DNA control transcription. Genetic variations in genes encoding histones, epigenetics-related enzymes or modifiers affect chromatin structure/dynamics and result in alterations in gene expression contributing to cancer development or progression. Gliomas are brain tumors frequently associated with epigenetics-related gene deregulation. We perform whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples to unravel epigenetic dysfunctions driving gliomagenesis. Based on the results of the integrative analysis of the acquired profiles, we create an atlas of active enhancers and promoters in benign and malignant gliomas. We explore these elements and intersect with Hi-C data to uncover molecular mechanisms instructing gene expression in gliomas.

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Integrative Modelling of Gene Expression and Digital Phenotypes to Describe Senescence in Wheat

Genes ◽

10.3390/genes12060909 ◽

2021 ◽

Vol 12 (6) ◽

pp. 909

Author(s):

Anyela Valentina Camargo Rodriguez

Keyword(s):

Gene Expression ◽

Regulatory Networks ◽

Molecular Mechanisms ◽

Developmental Stages ◽

Computational Modelling ◽

Plant Morphology ◽

Reproductive Organs ◽

Biological Trait ◽

Cereal Grain ◽

Plant Level

Senescence is the final stage of leaf development and is critical for plants’ fitness as nutrient relocation from leaves to reproductive organs takes place. Although senescence is key in nutrient relocation and yield determination in cereal grain production, there is limited understanding of the genetic and molecular mechanisms that control it in major staple crops such as wheat. Senescence is a highly orchestrated continuum of interacting pathways throughout the lifecycle of a plant. Levels of gene expression, morphogenesis, and phenotypic development all play key roles. Yet, most studies focus on a short window immediately after anthesis. This approach clearly leaves out key components controlling the activation, development, and modulation of the senescence pathway before anthesis, as well as during the later developmental stages, during which grain development continues. Here, a computational multiscale modelling approach integrates multi-omics developmental data to attempt to simulate senescence at the molecular and plant level. To recreate the senescence process in wheat, core principles were borrowed from Arabidopsis Thaliana, a more widely researched plant model. The resulted model describes temporal gene regulatory networks and their effect on plant morphology leading to senescence. Digital phenotypes generated from images using a phenomics platform were used to capture the dynamics of plant development. This work provides the basis for the application of computational modelling to advance understanding of the complex biological trait senescence. This supports the development of a predictive framework enabling its prediction in changing or extreme environmental conditions, with a view to targeted selection for optimal lifecycle duration for improving resilience to climate change.

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The secreted endoribonuclease ENDU-2 from the soma protects germline immortality in C. elegans

Nature Communications ◽

10.1038/s41467-021-21516-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Wenjing Qi ◽

Erika D. V. Gromoff ◽

Fan Xu ◽

Qian Zhao ◽

Wei Yang ◽

...

Keyword(s):

Gene Expression ◽

Stem Cell ◽

Small Rnas ◽

C Elegans ◽

Cleavage Activity ◽

Response To Temperature ◽

Multicellular Organisms ◽

Cell Immortality ◽

Mature Mrnas ◽

Endoribonuclease Activity

AbstractMulticellular organisms coordinate tissue specific responses to environmental information via both cell-autonomous and non-autonomous mechanisms. In addition to secreted ligands, recent reports implicated release of small RNAs in regulating gene expression across tissue boundaries. Here, we show that the conserved poly-U specific endoribonuclease ENDU-2 in C. elegans is secreted from the soma and taken-up by the germline to ensure germline immortality at elevated temperature. ENDU-2 binds to mature mRNAs and negatively regulates mRNA abundance both in the soma and the germline. While ENDU-2 promotes RNA decay in the soma directly via its endoribonuclease activity, ENDU-2 prevents misexpression of soma-specific genes in the germline and preserves germline immortality independent of its RNA-cleavage activity. In summary, our results suggest that the secreted RNase ENDU-2 regulates gene expression across tissue boundaries in response to temperature alterations and contributes to maintenance of stem cell immortality, probably via retaining a stem cell specific program of gene expression.

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Comparative neurotranscriptomics reveal widespread species differences associated with bonding

BMC Genomics ◽

10.1186/s12864-021-07720-0 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Joel A. Tripp ◽

Alejandro Berrio ◽

Lisa A. McGraw ◽

Mikhail V. Matz ◽

Jamie K. Davis ◽

...

Keyword(s):

Gene Expression ◽

Brain Region ◽

Molecular Mechanisms ◽

Species Differences ◽

Cell Structure ◽

Bond Formation ◽

Pair Bonding ◽

Prairie Voles ◽

Meadow Voles ◽

Time Points

Abstract Background Pair bonding with a reproductive partner is rare among mammals but is an important feature of human social behavior. Decades of research on monogamous prairie voles (Microtus ochrogaster), along with comparative studies using the related non-bonding meadow vole (M. pennsylvanicus), have revealed many of the neural and molecular mechanisms necessary for pair-bond formation in that species. However, these studies have largely focused on just a few neuromodulatory systems. To test the hypothesis that neural gene expression differences underlie differential capacities to bond, we performed RNA-sequencing on tissue from three brain regions important for bonding and other social behaviors across bond-forming prairie voles and non-bonding meadow voles. We examined gene expression in the amygdala, hypothalamus, and combined ventral pallidum/nucleus accumbens in virgins and at three time points after mating to understand species differences in gene expression at baseline, in response to mating, and during bond formation. Results We first identified species and brain region as the factors most strongly associated with gene expression in our samples. Next, we found gene categories related to cell structure, translation, and metabolism that differed in expression across species in virgins, as well as categories associated with cell structure, synaptic and neuroendocrine signaling, and transcription and translation that varied among the focal regions in our study. Additionally, we identified genes that were differentially expressed across species after mating in each of our regions of interest. These include genes involved in regulating transcription, neuron structure, and synaptic plasticity. Finally, we identified modules of co-regulated genes that were strongly correlated with brain region in both species, and modules that were correlated with post-mating time points in prairie voles but not meadow voles. Conclusions These results reinforce the importance of pre-mating differences that confer the ability to form pair bonds in prairie voles but not promiscuous species such as meadow voles. Gene ontology analysis supports the hypothesis that pair-bond formation involves transcriptional regulation, and changes in neuronal structure. Together, our results expand knowledge of the genes involved in the pair bonding process and open new avenues of research in the molecular mechanisms of bond formation.

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