Transcriptional landscape of pathogen-responsive lncRNAs in primary mammary epithelial cells reveals insights in immune response and defense mechanism.
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ABSTRACT:
ORGANISM(S): Capra hircus
PROVIDER: GSE167591 | GEO | 2022/01/25
REPOSITORIES: GEO
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Project description:Porcine circovirus type 2 (PCV2) can cause severe disease in the affected pigs, resulting in massive economic loss for the swine industry. Transcriptomics and proteomics approaches have been widely employed to identify the underlying molecular mechanisms of PCV2 infection. Numerous differentially expressed mRNAs, miRNAs, and proteins, together with their associated signaling pathways, have been identified, paving the way to further validation of their biological functions. Long non-coding RNA (lncRNA) is an important regulator of multiple biological processes. However, rare information regarding its role in the PCV2 infection has been obtained. Hence, in our study, RNA-seq was performed by infecting PK-15 cells with PCV2. Analysis of the differentially expressed genes (DEGs) suggested that cytoskeleton, apoptosis, cell division, and protein phosphorylation were significantly disturbed. Then, using stringent parameters, six lncRNAs were identified. Additionally, the potential targets of the lncRNAs were predicted using both cis- and trans-prediction methods. Interestingly, we found that the HOXB (Homeobox B) gene cluster was probably the target of the lncRNA LOC106505099. Enrichment analysis of the target genes showed that numerous developmental processes were altered during PCV2 infection. Therefore, our study revealed that lncRNAs could affect porcine embryo development through the regulation of the HOXB genes.
2020-06-19 | GSE149711 | GEO
Project description:Liver regeneration has important implications because many therapeutic strategies for the surgical treatment of liver diseases, such as removal of liver tumors and liver transplantation, depend on the ability of the liver to regenerate physically and functionally. Recent studies reported that lncRNAs control cell proliferation in hepatocellular carcinoma (HCC). However, the role of lncRNAs in liver regeneration and the overall mechanisms remain largely unknown. To address this issue, we carried out a genome-wide lncRNA microarray analysis during liver regeneration in mice after 2/3 partial hepatectomy (PH) at various time points. The results revealed differential expression of thousands of lncRNAs during liver regeneration. Six-week-old male wildtype C57Bl/6 mouse liver samples were obtained at 0, 1.5, 12, and 24 hours after 2/3 PH, and three mice were analyzed for each time point. Total RNA was isolated using Trizol.Mouse Stringent LncRNA Array (4 x 44K, ArrayStar, Rockville, MD) were used to monitor the expression level of approximately 14000 lncRNAs identified from the NCBI RefSeq, UCSC, RNAdb2.0, NRED, Fantom3.0 and UCRs. LncRNAs differentially expressed were identified by comparing expression levels during liver regeneration in mice after 2/3 partial hepatectomy (PH) at various time points.
2013-04-24 | E-GEOD-43687 | biostudies-arrayexpress
Project description:The gram- positive bacterial pathogen Clavibacter michiganensis subsp. michiganensis (Cmm) causes huge economic losses by infecting tomato plants worldwide. Cmm can be spread by contaminated seeds and transplants, penetrating the plant through natural openings or wounds and is transferred through the plant xylem. While in recent years significant progress has been made to elucidate plant responses to pathogenic gram-negative bacteria by gene expression studies, the molecular mechanisms that lead to disease symptoms caused by gram-positive bacteria like Cmm remain elusive. An indigenous virulent Cmm strain isolated from a farm crop of Pomodoro tomatoes in southern Greece was used for the infection of EKSTASIS F1 hybrid tomato seedlings. Here, we present the results of a deep RNA- sequencing (RNA-seq) analysis performed to characterize the dynamic expression profile of tomato genes upon Cmm infection.
2021-08-10 | GSE160971 | GEO
Project description:A vast portion of the mammalian genome is transcribed as long non-coding RNAs (lncRNAs) acting in the cytoplasm with largely unknown functions. Surprisingly, lncRNAs have been shown to interact with ribosomes, encode uncharacterized proteins, or act as ribosome sponges. These functions still remain mostly undetected and understudied owing to the lack of efficient tools for genome-wide simultaneous identification of ribosome-associated lncRNAs and peptide-producing lncRNAs. Here we present AHARIBO, a method for the detection of lncRNAs either untranslated, but associated with ribosomes, or encoding small peptides. Using AHARIBO in mouse embryonic stem cells during neuronal differentiation, we isolated ribosome-protected RNA fragments, translated RNAs and corresponding de novo synthesized polypeptides. Besides identifying mRNAs under active translation and associated ribosomes, we found and distinguished lncRNAs acting as ribosome sponges or encoding micropeptides, laying the ground for a better functional understanding of hundreds lncRNAs.
2021-09-09 | PXD022679 | Pride
Project description:Long non-coding RNAs (lncRNAs) are components of epigenetic control mechanisms that ensure appropriate and timely gene expression. The functions of lncRNAs are often mediated through associated gene regulatory activities, but how lncRNAs are distinguished from other RNAs and recruit effector complexes is unclear. Here we utilize the fission yeast Schizosaccharomyces pombe to investigate how lncRNAs engage silencing activities to regulate gene expression in cis. We find that invasion of lncRNA transcription into the downstream gene body incorporates a cryptic intron required for repression of that gene. Our analyses show that lncRNAs containing cryptic introns are targeted by the conserved Pir2ARS2 protein in association with splicing factors, which recruit RNA processing and chromatin modifying activities involved in gene silencing. Pir2 and splicing machinery are broadly required for gene repression. Our finding that human ARS2 also interacts with splicing factors suggests a conserved mechanism mediates gene repression through cryptic introns within lncRNAs.
2020-04-07 | PXD018373 | Pride
Project description:Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this study, we investigated the function of β cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis. This revealed lncRNAs that function in concert with transcription factors to regulate β cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key β cell transcription factor, and that both PLUTO and PDX1 are downregulated in islets from donors with type 2 diabetes or impaired glucose tolerance. These results implicate lncRNAs in the regulation of β cell-specific transcription factor networks.
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Project description:Small, compact genomes confer a selective advantage to viruses, yet human cytomegalovirus (HCMV) expresses the long non-coding RNAs (lncRNAs) RNA1.2, RNA2.7, RNA4.9, and RNA5.0. These lncRNAs account for majority of the viral transcriptome, but their functions remain largely unknown. Here, we showed that HCMV lncRNAs, except for RNA5.0, are required throughout the entire viral life cycle. Deletion of each lncRNA resulted in a decrease in viral progeny during lytic replication and failing to efficiently establish latent reservoirs and reactivate. Nanopore direct RNA sequencing of native lncRNA molecules revealed that each lncRNA exhibited a dynamic modification landscape, depending on the state of infection. Global analysis of the lncRNA interactome identified 32, 11, and 89 host factors that specifically bind to RNA1.2, RNA2.7, and RNA4.9, respectively. Moreover, 52 proteins commonly bound to the three lncRNAs were identified, including 11 antiviral immunity-related proteins. Our molecular analyses found that three lncRNAs are modified with N⁶-methyladenosine (m6A) and interact with m6A readers in all infection states. In-depth functional analysis revealed that m6A–mediated lncRNA stabilization as the key mechanism by which lncRNAs are maintained at high levels. Our study lays the groundwork for understanding viral lncRNA–mediated regulation of host-virus interaction throughout the HCMV life cycle.
2022-11-14 | PXD034587 | Pride
Project description:Functional studies of long noncoding RNAs (lncRNAs) have long been hindered by a lack of methods to assess their evolution. Here, we present lncHOME (lncRNA Homology Explorer), a computational pipeline that identifies a unique coPARSE-lncRNA class with conserved genomic locations and patterns of RNA binding protein (RBP) binding sites. Remarkably, several hundred human coPARSE-lncRNAs can be evolutionarily traced to zebrafish. Using CRISPR-Cas12a knockout and rescue assays, we found that knocking out many human coPARSE-lncRNAs led to cell proliferation defects that were rescued by predicted zebrafish homologs. Knocking down the coPARSE-lncRNAs in zebrafish embryos caused severe developmental delays that were rescued by human homologs. Moreover, we verified that human, mouse, and zebrafish coPARSE-lncRNA homologs tend to bind similar RBPs with their conserved fuctions relying on specific RBP binding sites. Overall, our study demonstrates a comprehensive approach for studying functional conservation of lncRNAs and implicates numerous lncRNAs in regulating cellular physiology.
2024-01-26 | PXD046452 | Pride
Project description:Background: Long non-coding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. They are aberrantly expressed in many types of diseases. We want to study the lncRNAs profiles in preeclampsia. Preeclampsia has been observed in patients with molar pregnancy where a fetus is absent demonstrating that the placenta is sufficient to cause the condition. So we analyze the lncRNAs profiles in preeclampsia placentas. In this study, we described the lncRNAs profiles in 6 preeclampsia placentas (T) and 5 matched normal pregnancy placentas (N) tissues by microarray. Methodology/Principal Findings: With abundant and varied probes accounting 33,045 LncRNAs in our microarray, the number of lncRNAs that expressed at a certain level could be detected is 28,443. From the data we found there were 738 lncRNAs that differentially expressed (M-bM-^IM-%1.5 fold-change) among preeclampsia placentas compared with matched controls. Up to 18,063 coding transcripts could be detected in placenta samples through 30,215 coding transcripts probes. Coding-non-coding gene co-expression networks (CNC network) were constructed based on the correlation analysis between the differential expressed lncRNAs and mRNAs. According to the GO-Pathway analysis of differential expressed lncRNAs/mRNAs, we choose three lncRNAs to analyze the relationship between lncRNAs and preeclampsia. LOC391533, LOC284100, CEACAMP8 were evaluated by qPCR in 40 of preeclampsia placentas and 40 of controls. The results showed three lncRNAs were aberrantly expressed in preeclampsia placentas compared with controls. Conclusions/Significance: Our study is the first one to determine genome-wide lncRNAs expression patterns in preeclampsia placenta by microarray. The results displayed that clusters of lncRNAs were aberrantly expressed in preeclampsia placenta compared with controls, which revealed that lncRNAs differentially expressed in preeclampsia placenta may exert a partial or key role in preeclampsia development. Misregulation of LOC391533, LOC284100, CEACAMP8 might be associated with preeclampsia. Taken together, this study may provide potential targets for future treatment of preeclampsia and novel insights into preeclampsia biology. LncRNAs/mRNAs profiles in 6 preeclampsia placentas and 5 matched normal pregnancy placentas tissues by microarray using Arraystar v2.0.
2013-09-12 | E-GEOD-50783 | biostudies-arrayexpress