Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA338698 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4020950.fastq.gz | Fastqsanger.gz | |||
| SRR4020949.fastq.gz | Fastqsanger.gz |
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Project description:The cellular accumulation of short non-coding RNAs (ncRNAs) transcribed by RNA Polymerase III (Pol III) is a hallmark of various cellular stressors and inflammatory-associated diseases. Yet, the mechanisms driving the accumulation of these RNAs are largely undefined. Infection with several DNA viruses is known to significantly alter the cellular Pol III transcriptome, leading to the induction of a class of non-coding retrotransposons known as short interspersed nuclear elements (SINE) and tRNA genes. Here, we sought to define the mechanisms driving Pol III transcribed ncRNA abundance during viral infection, using the murine herpesvirus MHV68 as a model. Our findings reveal that while the expression of Pol III transcripts, such as the murine-specific family of B2 SINE ncRNAs and pre-tRNAs, significantly increase during MHV68 infection, Pol III genomic occupancy is enhanced at a much fewer subset of B2 SINE and tRNA genes. Using DNA motif analyses and a convolutional neural network (CNN) based model, we identified non-promoter sequence elements within B2 SINE genes that distinguish infection-induced loci. We found that infection-induced B2 SINE genes are enriched for signal sequences that confer polyadenylation, and endogenous B2 SINE ncRNA polyadenylation depends on mRNA cleavage and polyadenylation (CPSF) machinery. We discovered that mRNA CPSF components are recruited to sites of Pol III transcription in response to MHV68 infection in a manner dependent on Pol III occupancy. Chromatin-associated B2 SINE ncRNAs are also bound by the CPSF complex, suggesting an RNA-dependent, co-transcriptional polyadenylation of B2 SINE ncRNAs. This uncovers an inducible, coupled relationship between Pol III transcription and mRNA-like polyadenylation of ncRNAs. Also, CPSF recruitment to Pol III genes is not restricted to murine genomes but also occurs at human SINE and tRNA genes, suggesting that this previously unknown coupled relationship may be a widespread feature of Pol III transcription.
2025-03-10 | GSE288677 | GEO
Project description:We identified a novel long non-coding RNA Lx8-SINE B2, that is a marker of pluripotency. Depletion of Lx8-SINE B2 impacts embryonic stem cell self-renewal. RNA-seq analysis of Lx8-SINE B2 depletion revealed that a number of glycolytic genes with decreased expression. Mechanistically, we found that the Lx8-SINE B2 activates the glycolysis pathway by binding to Eno1. Collectively, our data suggest that Lx8-SINE B2 maintains the self-renewal of mESCs through glycolysis.
2022-09-19 | GSE182247 | GEO
Project description:Short interspersed nuclear elements (SINEs) are retrotransposons evolutionarily derived from endogenous RNA Polymerase III RNAs. Though SINE elements have undergone exaptation into gene regulatory elements, how transcribed SINE RNA impacts transcriptional and post-transcriptional regulation is largely unknown. This is partly due to a lack of information regarding which of the loci have transcriptional potential. Here, we present an approach (short interspersed nuclear element sequencing, SINE-seq), which selectively profiles RNA Polymerase III-derived SINE RNA, thereby identifying transcriptionally active SINE loci. Applying SINE-seq to monitor murine B2 SINE expression during a gammaherpesvirus infection revealed transcription from 28,270 SINE loci, with ~50% of active SINE elements residing within annotated RNA Polymerase II loci. Furthermore, B2 RNA can form intermolecular RNA-RNA interactions with complementary mRNAs, leading to nuclear retention of the targeted mRNA via a mechanism involving p54nrb. These findings illuminate a pathway for the selective regulation of mRNA export during stress via retrotransposon activation.
2016-10-31 | GSE85518 | GEO
Project description:We report the comparison between SINE B2-AS transcriptome profiling and Dicer1-deficient-cell transcriptome profiling using RNA-seq analysis. We report that thousands of SINE B2 copies encode long B2-AS transcripts, which are constantly degraded by Dicer1. This new class of B2-AS transcripts regulates the expression of SINE B2 sense (B2-S) transcripts. Long B2-S is the main cause of cellular toxicity likely mediated by the multifunctional protein TSPO. Some B2-AS transcripts are putative miRNAs interconnected with the RNAi system. We propose that B2-AS transcripts have evolved as a self-defense mechanism to subvert the host RNAi system.
2020-09-01 | GSE126041 | GEO
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
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Project description:Prior analysis suggsted that that AP-1 TFs play a role in expression of specific B2-SINE following in-vivo nerve injury. We thus sought to experimnetally test the role of AP-1 transcription factors in upregulation of B2-SINE RNA expression in DRG neurons. Neurons were transduced with PHP.S-AAV vectors expressing either A-Fos (dominant negative construct that targets Fos-interacting transcription factors), GFP control or were left untransduced. RNA was extracted 7 days later and analyzed to identify effects on B2-SINE expression and known AP-1 targetted mRNAs.
2025-05-16 | GSE230719 | GEO
Project description:Translational research is commonly performed in the C57B6/J mouse strain, chosen for its genetic homogeneity and phenotypic uniformity. Here, we evaluate the suitability of the white-footed deer mouse (Peromyscus leucopus) as a model organism for aging research, offering a comparative analysis against C57B6/J and diversity outbred (DO) Mus musculus strains. Our study includes comparisons of body composition, skeletal muscle function, and cardiovascular parameters, shedding light on potential applications and limitations of P. leucopus in aging studies. Notably, P. leucopus exhibits distinct body composition characteristics, emphasizing reduced muscle force exertion and a unique metabolism, particularly in fat mass. Cardiovascular assessments showed changes in arterial stiffness, challenging conventional assumptions and highlighting the need for a nuanced interpretation of aging-related phenotypes. Our study also highlights inherent challenges associated with maintaining and phenotyping P. leucopus cohorts. Behavioral considerations, including anxiety-induced responses during handling and phenotyping assessment, pose obstacles in acquiring meaningful data. Moreover, the unique anatomy of P. leucopus necessitates careful adaptation of protocols designed for Mus musculus. While showcasing potential benefits, further extensive analyses across broader age ranges and larger cohorts are necessary to establish the reliability of P. leucopus as a robust and translatable model for aging studies.
| S-EPMC11335981 | biostudies-literature
Project description:More than one million copies of short interspersed elements (SINEs), a class of retrotransposons, are present in the mammalian genomes, particularly within gene-rich genomic regions. Evidence has accumulated that ancient SINE sequences have acquired new binding sites for transcription factors (TFs) through multiple mutations following retrotransposition, and as a result have rewired the host regulatory network during the course of evolution. However, it remains unclear whether currently active SINEs contribute to the expansion of TF binding sites. To study the mobility, expression, and function of SINE copies, we first identified about 2,000 insertional polymorphisms of B1 and B2 SINE families within Mus musculus. Using a novel RNA sequencing method developed here, we detected the expression of SINEs in testes at both the subfamily and genomic copy levels: the vast majority of B1 RNAs originated from evolutionarily young subfamilies, whereas B2 RNAs contained transcripts from both young and old subfamilies. DNA methylation and chromatin immunoprecipitation-sequencing (ChIP-seq) analyses revealed that polymorphic B2 insertions served as a chromatin boundary element inhibiting the expansion of DNA hypomethylated and histone hyperacetylated regions, and decreased the expression of neighboring genes. Moreover, a total of > 100 polymorphic B2 insertions were bound by CTCF, a well-known chromatin boundary protein. These results suggest that the currently active B2 copies are mobile chromatin boundary elements that can modulate gene expression level, and are likely involved in epigenomic and phenotypic diversification of the mouse species.
2021-05-26 | GSE156316 | GEO
Project description:BackgroundCopy number variation is an important dimension of genetic diversity and has implications in development and disease. As an important model organism, the mouse is a prime candidate for copy number variant (CNV) characterization, but this has yet to be completed for a large sample size. Here we report CNV analysis of publicly available, high-density microarray data files for 351 mouse tail samples, including 290 mice that had not been characterized for CNVs previously.ResultsWe found 9634 putative autosomal CNVs across the samples affecting 6.87% of the mouse reference genome. We find significant differences in the degree of CNV uniqueness (single sample occurrence) and the nature of CNV-gene overlap between wild-caught mice and classical laboratory strains. CNV-gene overlap was associated with lipid metabolism, pheromone response and olfaction compared to immunity, carbohydrate metabolism and amino-acid metabolism for wild-caught mice and classical laboratory strains, respectively. Using two subspecies of wild-caught Mus musculus, we identified putative CNVs unique to those subspecies and show this diversity is better captured by wild-derived laboratory strains than by the classical laboratory strains. A total of 9 genic copy number variable regions (CNVRs) were selected for experimental confirmation by droplet digital PCR (ddPCR).ConclusionThe analysis we present is a comprehensive, genome-wide analysis of CNVs in Mus musculus, which increases the number of known variants in the species and will accelerate the identification of novel variants in future studies.
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Project description:BackgroundLong terminal repeat (LTR) retrotransposons make up a large fraction of the typical mammalian genome. They comprise about 8% of the human genome and approximately 10% of the mouse genome. On account of their abundance, LTR retrotransposons are believed to hold major significance for genome structure and function. Recent advances in genome sequencing of a variety of model organisms has provided an unprecedented opportunity to evaluate better the diversity of LTR retrotransposons resident in eukaryotic genomes.ResultsUsing a new data-mining program, LTR_STRUC, in conjunction with conventional techniques, we have mined the GenBank mouse (Mus musculus) database and the more complete Ensembl mouse dataset for LTR retrotransposons. We report here that the M. musculus genome contains at least 21 separate families of LTR retrotransposons; 13 of these families are described here for the first time.ConclusionsAll families of mouse LTR retrotransposons are members of the gypsy-like superfamily of retroviral-like elements. Several different families of unrelated non-autonomous elements were identified, suggesting that the evolution of non-autonomy may be a common event. High sequence similarity between several LTR retrotransposons identified in this study and those found in distantly-related species suggests that horizontal transfer has been a significant factor in the evolution of mouse LTR retrotransposons.
| S-EPMC395764 | biostudies-literature