scholarly journals An ancient retroviral RNA element hidden in mammalian genomes and its involvement in co-opted retroviral gene regulation

Retrovirology ◽  
2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Koichi Kitao ◽  
So Nakagawa ◽  
Takayuki Miyazawa
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Endogenous Retroviruses ◽  
Sequence Motifs ◽  
Specific Sequence ◽  
Rna Regulation ◽  
Mammalian Genomes ◽  
Rna Elements ◽  
Viral Sequences

Abstract Background Retroviruses utilize multiple unique RNA elements to control RNA processing and translation. However, it is unclear what functional RNA elements are present in endogenous retroviruses (ERVs). Gene co-option from ERVs sometimes entails the conservation of viral cis-elements required for gene expression, which might reveal the RNA regulation in ERVs. Results Here, we characterized an RNA element found in ERVs consisting of three specific sequence motifs, called SPRE. The SPRE-like elements were found in different ERV families but not in any exogenous viral sequences examined. We observed more than a thousand of copies of the SPRE-like elements in several mammalian genomes; in human and marmoset genomes, they overlapped with lineage-specific ERVs. SPRE was originally found in human syncytin-1 and syncytin-2. Indeed, several mammalian syncytin genes: mac-syncytin-3 of macaque, syncytin-Ten1 of tenrec, and syncytin-Car1 of Carnivora, contained the SPRE-like elements. A reporter assay revealed that the enhancement of gene expression by SPRE depended on the reporter genes. Mutation of SPRE impaired the wild-type syncytin-2 expression while the same mutation did not affect codon-optimized syncytin-2, suggesting that SPRE activity depends on the coding sequence. Conclusions These results indicate multiple independent invasions of various mammalian genomes by retroviruses harboring SPRE-like elements. Functional SPRE-like elements are found in several syncytin genes derived from these retroviruses. This element may facilitate the expression of viral genes, which were suppressed due to inefficient codon frequency or repressive elements within the coding sequences. These findings provide new insights into the long-term evolution of RNA elements and molecular mechanisms of gene expression in retroviruses.

scholarly journals An ancient retroviral RNA element hidden in mammalian genomes and its involvement in coopted retroviral gene regulation

2021 ◽  
Author(s):  
Koichi Kitao ◽  
So Nakagawa ◽  
Takayuki Miyazawa
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Rna Processing ◽  
Endogenous Retroviruses ◽  
Wild Type ◽  
Mammalian Genomes ◽  
Rna Elements ◽  
Negative Factors ◽  
Viral Sequences

AbstractRetroviruses utilize multiple unique RNA elements to control several aspects of RNA processing, such as splicing, subcellular export, and translation. However, it is mostly unclear whether such functional RNA elements are present in endogenous retroviruses (ERVs), many of which were inserted into the host genomes millions of years ago. Previously, in human ERV-derived syncytin-1 gene, we found a cis-acting RNA element named SPRE that enhances its protein expression. In this study, we found a 17-nt common sequence in SPRE of syncytin-1 and another ERV-derived gene, syncytin-2, and the sequence is confirmed to be essential for the expression of the proteins. We detected the sequences of SPRE-like elements in 41 ERV families. Though the SPRE-like elements were not found in currently prevailing (i.e. exogenous) viral sequences, more than thousands of copies of the elements were found in several mammalian genomes, suggesting the ancient integration and propagation of the SPRE-harboring retroviruses in mammalian lineages. Indeed, other mammalian ERV-derived genes: mac-syncytin-3 of macaque, syncytin-Ten1 of tenrec, and syncytin-Car1 of Carnivora contain the SPRE-like elements, and we validated their function for efficient protein expression by in vitro assays. A reporter assay revealed that the enhancement of gene expression by SPRE depended on reporter genes. Moreover, the mutation in SPRE did not affect the gene expression in codon-optimized syncytin-2. However, the same mutation in SPRE impaired the gene expression in wild-type syncytin-2, suggesting that the SPRE dependency of Syncytin-2 expression is due to the negative factors such as inefficient codon frequency or repressive elements within the coding sequence. These results provide new implications that ERVs harbor unique RNA elements involved in the regulation of ERV-derived genes.

scholarly journals Tracking interspecies transmission and long-term evolution of an ancient retrovirus using the genomes of modern mammals

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
William E Diehl ◽  
Nirali Patel ◽  
Kate Halm ◽  
Welkin E Johnson
Keyword(s):  
Fossil Record ◽  
Viral Infections ◽  
Endogenous Retroviruses ◽  
Interspecies Transmission ◽  
Viral Spread ◽  
Protein Functions ◽  
History Of ◽  
Mammalian Genomes ◽  
Retroviral Infections

Mammalian genomes typically contain hundreds of thousands of endogenous retroviruses (ERVs), derived from ancient retroviral infections. Using this molecular 'fossil' record, we reconstructed the natural history of a specific retrovirus lineage (ERV-Fc) that disseminated widely between ~33 and ~15 million years ago, corresponding to the Oligocene and early Miocene epochs. Intercontinental viral spread, numerous instances of interspecies transmission and emergence in hosts representing at least 11 mammalian orders, and a significant role for recombination in diversification of this viral lineage were also revealed. By reconstructing the canonical retroviral genes, we identified patterns of adaptation consistent with selection to maintain essential viral protein functions. Our results demonstrate the unique potential of the ERV fossil record for studying the processes of viral spread and emergence as they play out across macro-evolutionary timescales, such that looking back in time may prove insightful for predicting the long-term consequences of newly emerging viral infections.

scholarly journals Transcriptome-wide gene expression plasticity in Stipa grandis in response to grazing intensity differences

2020 ◽  
Author(s):  
Zhenhua Dang ◽  
Yuanyuan Jia ◽  
Yunyun Tian ◽  
Jiabin Li ◽  
Yanan Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Grazing Intensity ◽  
Glycolate Oxidase ◽  
Bisphosphate Carboxylase ◽  
Grazing Intensities

Organisms have evolved effective and distinct adaptive strategies to survive. Stipa grandis is one of the widespread dominant species on the typical steppe of the Inner Mongolian Plateau, and is regarded as a suitable species for studying the effects of grazing in this region. Although phenotypic (morphological and physiological) variations in S. grandis in response to long-term grazing have been identified, the molecular mechanisms underlying adaptations and plastic responses remain largely unknown. Accordingly, we performed a transcriptomic analysis to investigate changes in gene expression of S. grandis under four different grazing intensities. A total of 2,357 differentially expressed genes (DEGs) were identified among the tested grazing intensities, suggesting long-term grazing resulted in gene expression plasticity that affected diverse biological processes and metabolic pathways in S. grandis. DEGs were identified that indicated modulation of Calvin–Benson cycle and photorespiration metabolic pathways. The key gene´expression profiles encoding various proteins (e.g., Ribulose-1,5-bisphosphate carboxylase/oxygenase, fructose-1,6-bisphosphate aldolase, glycolate oxidase etc.) involved in these pathways suggest that they may synergistically respond to grazing to increase the resilience and stress tolerance of S. grandis. Our findings provide scientific clues for improving grassland use and protection, and identify important questions to address in future transcriptome studies.

scholarly journals Transcriptional signatures throughout development: the effects of mouse embryo manipulation in vitro

Reproduction ◽  
2017 ◽  
Vol 153 (1) ◽  
pp. 107-122 ◽  
Author(s):  
Sky K Feuer ◽  
Xiaowei Liu ◽  
Annemarie Donjacour ◽  
Rhodel Simbulan ◽  
Emin Maltepe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Preimplantation Embryo ◽  
Environmental Exposures ◽  
Developmental Time ◽  
Transcriptional Responses ◽  
Transcriptional Changes ◽  
Specific Impact

Stressful environmental exposures incurred early in development can affect postnatal metabolic health and susceptibility to non-communicable diseases in adulthood, although the molecular mechanisms by which this occurs have yet to be elucidated. Here, we use a mouse model to investigate how assortedin vitroexposures restricted exclusively to the preimplantation period affect transcription both acutely in embryos and long term in subsequent offspring adult tissues, to determine if reliable transcriptional markers ofin vitrostress are present at specific developmental time points and throughout development. Eachin vitrofertilization or embryo culture environment led to a specific and unique blastocyst transcriptional profile, but we identified a common 18-gene and 9-pathway signature of preimplantation embryo manipulation that was present in allin vitroembryos irrespective of culture condition or method of fertilization. This fingerprint did not persist throughout development, and there was no clear transcriptional cohesion between adult IVF offspring tissues or compared to their preceding embryos, indicating a tissue-specific impact ofin vitrostress on gene expression. However, the transcriptional changes present in each IVF tissue were targeted by the same upstream transcriptional regulators, which provide insight as to how acute transcriptional responses to stressful environmental exposures might be preserved throughout development to influence adult gene expression.

scholarly journals PyBoost: A parallelized Python implementation of 2D boosting with hierarchies

2017 ◽  
Author(s):  
Peyton G. Greenside ◽  
Nadine Hussami ◽  
Jessica Chang ◽  
Anshul Kundaje
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Stem Cell Differentiation ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Sequence Motifs ◽  
Specific Sequence ◽  
Tail Regeneration ◽  
Perturbation Data ◽  
Time Courses

AbstractMotivation:Gene expression is controlled by networks of transcription factors that bind specific sequence motifs in regulatory DNA elements such as promoters and enhancers. GeneClass is a boosting-based algorithm that learns gene regulatory networks from complementary paired feature sets such as transcription factor expression levels and binding motifs across conditions. This algorithm can be used to predict functional genomics measures of cell state, such as gene expression and chromatin accessibility, in different cellular conditions. We present a parallelized, Python-based implementation of GeneClass, called PyBoost, along with a novel hierarchical implementation of the algorithm, called HiBoost. HiBoost allows regulatory logic to be constrained to a hierarchical group of conditions or cell types. The software can be used to dissect differentiation cascades, time courses or other perturbation data that naturally form a hierarchy or trajectory. We demonstrate the application of PyBoost and HiBoost to learn regulators of tadpole tail regeneration and hematopoeitic stem cell differentiation and validate learned regulators through an inducible CRISPR system.Availability:The implementation is publicly available here:https://github.com/kundajelab/boosting2D/.

scholarly journals 6S RNA Function Enhances Long-Term Cell Survival

2004 ◽  
Vol 186 (15) ◽  
pp. 4978-4985 ◽  
Author(s):  
Amy E. Trotochaud ◽  
Karen M. Wassarman
Keyword(s):  
Stationary Phase ◽  
Molecular Mechanisms ◽  
Physiological Role ◽  
Rna Regulation ◽  
Competitive Fitness ◽  
Growth Defects ◽  
6S Rna ◽  
Rna Inhibition

ABSTRACT 6S RNA was identified in Escherichia coli >30 years ago, but the physiological role of this RNA has remained elusive. Here, we demonstrate that 6S RNA-deficient cells are at a disadvantage for survival in stationary phase, a time when 6S RNA regulates transcription. Growth defects were most apparent as a decrease in the competitive fitness of cells lacking 6S RNA. To decipher the molecular mechanisms underlying the growth defects, we have expanded studies of 6S RNA effects on transcription. 6S RNA inhibition of σ70-dependent transcription was not ubiquitous, in spite of the fact that the vast majority of σ70-RNA polymerase is bound by 6S RNA during stationary phase. The σ70-dependent promoters inhibited by 6S RNA contain an extended −10 promoter element, suggesting that this feature may define a class of 6S RNA-regulated genes. We also discovered a secondary effect of 6S RNA in the activation of σS-dependent transcription at several promoters. We conclude that 6S RNA regulation of both σ70 and σS activities contributes to increased cell persistence during nutrient deprivation.

scholarly journals Mitochondrial RNA and its eccentricities

2015 ◽  
Vol 37 (2) ◽  
pp. 28-32
Author(s):  
Zofia M. ChrzanowskaLightowlers
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Maternal Inheritance ◽  
Mitochondrial Gene ◽  
Mitochondrial Rna ◽  
Mitochondrial Gene Expression ◽  
Mitochondrial Evolution ◽  
Inheritance Patterns ◽  
Rna Elements

For those who do not work on mitochondria, their knowledge is often restricted to eubacterial origins, production of ATP and perhaps an appreciation of the non-Mendelian maternal inheritance patterns. These features are true enough, but things then start to get more complicated. Although the origins of mitochondria are accepted as a eubacterial endosymbiont of evolving eukaryotic cells1, there were organisms that were described as having jettisoned these ‘organelles’, referred to as amitochondriate eukaryotes. This concept has been challenged, and rudimentary mitochondria, or mitosomes, have now been found in those eukaryotes, which are apparently reluctant to lose this organelle2. The consequences of mitochondrial evolution can be seen in the divergence from the standard repertoire of RNA elements. These eccentricities pose challenges to our understanding of molecular mechanisms underlying mitochondrial gene expression.

scholarly journals Comparative Transcriptome Analysis Provides Insights into The Response of Ulva Compressa to The Fluctuating Salinity Conditions

2020 ◽  
Author(s):  
Qikun Xing ◽  
Guiqi Bi ◽  
Min Cao ◽  
Arnaud Belcour ◽  
Méziane Aite ◽  
...  
Keyword(s):  
Gene Expression ◽  
Salinity Stress ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Green Tide ◽  
Saline Stress ◽  
Ulva Compressa ◽  
A Genome ◽  
Differently Expressed Genes

Abstract Background: Ulva compressa, known as the green tide forming species, was reported that can adapt to hypo-salinity conditions such as estuaries and brackish lakes. To understand the underlying molecular mechanisms of hypo-salinity stress tolerance, a genome-wide gene expression profiles in U. compressa was performed using digital gene expression profile (DGE). Results: The RNA-seq data were analyzed based on the comparison of differently expressed genes involved in specific pathways under hypo-salinity and recovery conditions. Under the long-term hypo-salinity stress, the recovery of photosynthesis and energy metabolism could provide sufficient energy for the tolerance under long-term hypo-saline stress. Multiple strategies were performed to maintain the osmotic homeostasis. Additionally, several long non-coding RNA were detected as differently expressed genes during the stress, which could play important roles in the osmotolerance. Conclusions: Our work will serve as an essential foundation for the understanding of the tolerance mechanism of U. compressa under the fluctuating salinity conditions.

scholarly journals Inhibition of RANKL and Sema4d Improves Residual Ridge Resorption in Mice.

2022 ◽  
Author(s):  
Meri Hisamoto ◽  
Shunsuke Kimura ◽  
Kai Iwata ◽  
Toshihiko Iwanaga ◽  
Atsuro Yokoyama
Keyword(s):  
Gene Expression ◽  
Bone Loss ◽  
Molecular Mechanisms ◽  
Alveolar Bone ◽  
Alveolar Bone Loss ◽  
Period Gene ◽  
Semaphorin 4D ◽  
Long Time ◽  
Extraction Model

Abstract Residual ridge resorption (RRR) is a chronic and progressive bone resorption following tooth loss. It causes deterioration of the oral environments and leads to the pathogenesis of various systemic diseases. However, the molecular mechanisms and risk factors for RRR progression are still unclear and controversial. In this study, we developed a tooth extraction model using mice for analyzing long-term morphological and gene expression changes in the alveolar bone. We further applied ovariectomy to this model to elucidate the effects of osteoporosis on RRR progression. As a result, the alveolar bone loss was biphasic and consisted of rapid loss in the early stages and subsequently slow and sustained bone loss over a long period. Gene expression analysis indicated that ovariectomy increased the expression of pro-inflammatory cytokines in the alveolar bone and prolonged the activation of osteoclasts same as histological analysis. Furthermore, the expressions of Tnfsf11 and Sema4d kept increasing for a long time in OVX mice. Administration of neutralization antibodies for receptor activator of NF-κB ligand (RANKL) effectively suppressed RRR. Similarly, inhibition of Semaphorin 4d (Sema4d) also improved alveolar bone loss. This study demonstrated that osteoporosis is a risk factor for RRR and that RANKL and Sema4d suppression are potential treatments.

scholarly journals Distribution, Diversity, and Evolution of Endogenous Retroviruses in Perissodactyl Genomes

2018 ◽  
Vol 92 (23) ◽  
Author(s):  
Henan Zhu ◽  
Robert James Gifford ◽  
Pablo Ramiro Murcia
Keyword(s):  
Germ Line ◽  
Mammalian Species ◽  
Endogenous Retroviruses ◽  
Functional Roles ◽  
Physiological Processes ◽  
Great Utility ◽  
White Rhinoceros ◽  
History Of ◽  
Mammalian Genomes

ABSTRACTThe evolution of mammalian genomes has been shaped by interactions with endogenous retroviruses (ERVs). In this study, we investigated the distribution and diversity of ERVs in the mammalian orderPerissodactyla, with a view to understanding their impact on the evolution of modern equids (familyEquidae). We characterize the major ERV lineages in the horse genome in terms of their genomic distribution, ancestral genome organization, and time of activity. Our results show that subsequent to their ancestral divergence from rhinoceroses and tapirs, equids acquired four novel ERV lineages. We show that two of these ERV lineages proliferated extensively in the lineage leading to modern horses, and one contains loci that are actively transcribed in specific tissues. In addition, we show that the white rhinoceros has resisted germ line colonization by retroviruses for more than 54 million years—longer than any other extant mammalian species. The map of equine ERVs that we provide here will be of great utility to future studies aiming to investigate the potential functional roles of equine ERVs and their impact on equine evolution.IMPORTANCEERVs in the host genome are highly informative about the long-term interactions of retroviruses and hosts. They are also interesting because they have influenced the evolution of mammalian genomes in various ways. In this study, we derive a calibrated timeline describing the process through which ERV diversity has been generated in the equine germ line. We determined the distribution and diversity of perissodactyl ERV lineages and inferred their retrotranspositional activity during evolution, thereby gaining insight into the long-term coevolutionary history of retroviruses and mammals. Our study provides a platform for future investigations to identify equine ERV loci involved in physiological processes and/or pathological conditions.

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