scholarly journals Novel endogenous retrovirus-derived transcript expressed in the bovine placenta is regulated by WNT signaling

2017 ◽  
Vol 474 (20) ◽  
pp. 3499-3512 ◽  
Author(s):  
Toshihiro Sakurai ◽  
So Nakagawa ◽  
Hanako Bai ◽  
Rulan Bai ◽  
Kazuya Kusama ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Expression Profiles ◽  
Evolutionary Process ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Individual Species ◽  
Placental Development ◽  
Proviral Sequence ◽  
Morphological Variations ◽  
Bovine Placenta

Endogenous retroviruses (ERVs) are involved in placentation; perhaps, the most well-known ERVs are the syncytins, actively transcribed env genes involved in cell–cell fusion and possible morphological variations. However, ERVs other than syncytins that play an important role in placental development have not been well characterized. To identify ERV genes expressed during the onset of placentation in the bovine species, we characterized the expression profiles of bovine conceptus transcripts during the peri-attachment period using RNA-seq analysis, and confirming some candidates through real-time PCR. Using in silico and PCR analyses, we identified a novel ERV proviral sequence derived from a gag region, designated bovine endogenous retroviruses (BERV)-K3, containing Gag_p10 and Gag_p24, zinc finger domain. Initial expression of this ERV in bovine conceptuses was on day 20 (day 0 = day of estrus), soon after conceptus attachment to the endometrial epithelium, and its high placental expression was maintained up to the middle of pregnancy. The BERV-K3 transcript was also found in the uterine luminal and glandular epithelia, liver, kidney, intestine, and skin. BERV-K3 is located on chromosome 7 and integrated within LOC100848658, from which noncoding RNA could be transcribed. Furthermore, the expression of endogenous BERV-K3 in bovine trophoblast cell lines was induced by a WNT agonist, a signaling system common to genes expressed in placentas. These data support the argument that during the evolutionary process, mammals incorporated not only similar ERV sequences, but also ERVs unique to individual species. BERV-K3 is in the latter case, likely providing functions unique to ruminant gestation.

scholarly journals Human Endogenous Retrovirus Expression Profiles in Samples from Brains of Patients with Schizophrenia and Bipolar Disorders

2005 ◽  
Vol 79 (17) ◽  
pp. 10890-10901 ◽  
Author(s):  
Oliver Frank ◽  
Michelle Giehl ◽  
Chun Zheng ◽  
Rüdiger Hehlmann ◽  
Christine Leib-Mösch ◽  
...  
Keyword(s):  
Genetic Background ◽  
Expression Profiles ◽  
Bipolar Disorders ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retrovirus ◽  
Pcr Analysis ◽  
Recent Onset ◽  
Detection And Identification ◽  
Neuropsychiatric Diseases

ABSTRACT The detection and identification of retroviral transcripts in brain samples, cerebrospinal fluid, and plasma of individuals with recent-onset schizophrenia and schizoaffective disorders suggest that activation or upregulation of distinct human endogenous retroviruses (HERVs) may play a role in the etiopathogenesis of neuropsychiatric diseases. To test this hypothesis, we performed a comprehensive microarray-based analysis of HERV transcriptional activity in human brains. We investigated 50 representative members of 20 HERV families in a total of 215 brain samples derived from individuals with schizophrenia or bipolar disorders and matched controls. A characteristic brain-specific retroviral activity profile was found that consists of members of the class I families HERV-E, HERV-F, and ERV9 and members of HERV-K taxa. In addition to these constitutively expressed HERVs, a number of differentially active HERV elements were identified in all brain samples independent of the disease pattern that may reflect differences in the genetic background of the tested individuals. Only a subgroup of the HML-2 family (HERV-K10) was significantly overrepresented in both bipolar-disorder- and schizophrenia-associated samples compared to healthy brains, suggesting a potential association with disease. Real-time PCR analysis of HERV env transcripts with coding capacity potentially involved in neuroinflammatory conditions revealed that env expression of HERV-W, HERV-FRD, and HML-2 remains unaffected regardless of the clinical picture. Our data suggest that HERV transcription in brains is weakly correlated with schizophrenia and related diseases but may be influenced by the individual genetic background, brain-infiltrating immune cells, or medical treatment.

scholarly journals Noncanonical immune response to the inhibition of DNA methylation by Staufen1 via stabilization of endogenous retrovirus RNAs

2021 ◽  
Vol 118 (13) ◽  
pp. e2016289118
Author(s):  
Yongsuk Ku ◽  
Joo-Hwan Park ◽  
Ryeongeun Cho ◽  
Yongki Lee ◽  
Hyoung-Min Park ◽  
...  
Keyword(s):  
Immune Response ◽  
Posttranscriptional Regulation ◽  
Noncoding Rna ◽  
Dna Methyltransferase ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Clinical Patient ◽  
Dna Methyltransferase Inhibitors ◽  
A Genome ◽  
Dsrna Binding Protein

DNA-methyltransferase inhibitors (DNMTis), such as azacitidine and decitabine, are used clinically to treat myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Decitabine activates the transcription of endogenous retroviruses (ERVs), which can induce immune response by acting as cellular double-stranded RNAs (dsRNAs). Yet, the posttranscriptional regulation of ERV dsRNAs remains uninvestigated. Here, we find that the viral mimicry and subsequent cell death in response to decitabine require the dsRNA-binding protein Staufen1 (Stau1). We show that Stau1 directly binds to ERV RNAs and stabilizes them in a genome-wide manner. Furthermore, Stau1-mediated stabilization requires a long noncoding RNA TINCR, which enhances the interaction between Stau1 and ERV RNAs. Analysis of a clinical patient cohort reveals that MDS and AML patients with lower Stau1 and TINCR expressions exhibit inferior treatment outcomes to DNMTi therapy. Overall, our study reveals the posttranscriptional regulatory mechanism of ERVs and identifies the Stau1-TINCR complex as a potential target for predicting the efficacy of DNMTis and other drugs that rely on dsRNAs.

scholarly journals The endogenous retrovirus-derived long noncoding RNA TROJAN promotes triple-negative breast cancer progression via ZMYND8 degradation

2019 ◽  
Vol 5 (3) ◽  
pp. eaat9820 ◽  
Author(s):  
Xi Jin ◽  
Xiao-En Xu ◽  
Yi-Zhou Jiang ◽  
Yi-Rong Liu ◽  
Wei Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Triple Negative ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Clinical Samples

Human endogenous retroviruses (HERVs) play pivotal roles in the development of breast cancer. However, the detailed mechanisms of noncoding HERVs remain elusive. Here, our genome-wide transcriptome analysis of HERVs revealed that a primate long noncoding RNA, which we dubbed TROJAN, was highly expressed in human triple-negative breast cancer (TNBC). TROJAN promoted TNBC proliferation and invasion and indicated poor patient outcomes. We further confirmed that TROJAN could bind to ZMYND8, a metastasis-repressing factor, and increase its degradation through the ubiquitin-proteasome pathway by repelling ZNF592. TROJAN also epigenetically up-regulated metastasis-related genes in multiple cell lines. Correlations between TROJAN and ZMYND8 were subsequently confirmed in clinical samples. Furthermore, our study verified that antisense oligonucleotide therapy targeting TROJAN substantially suppressed TNBC progression in vivo. In conclusion, the long noncoding RNA TROJAN promotes TNBC progression and serves as a potential therapeutic target.

scholarly journals Lack of antibody response in pigs immunized with the transmembrane envelope protein of porcine endogenous retroviruses

2014 ◽  
Vol 95 (8) ◽  
pp. 1827-1831 ◽  
Author(s):  
Martina Keller ◽  
Björn Petersen ◽  
Heiner Niemann ◽  
Joachim Denner
Keyword(s):  
Neutralizing Antibodies ◽  
Mammalian Species ◽  
Neutralization Assay ◽  
Endogenous Retrovirus ◽  
Proximal Region ◽  
Endogenous Retroviruses ◽  
Placental Development ◽  
Porcine Endogenous Retrovirus ◽  
Porcine Endogenous Retroviruses ◽  
Protein P15e

Recently, we immunized different mammalian species (goats, mice, rats, rabbits, guinea pigs and hamsters) with the recombinant ectodomain of the transmembrane envelope (TM) protein p15E of porcine endogenous retrovirus (PERV). In all cases, neutralizing immune sera were induced, which recognized epitopes in the fusion peptide proximal region and the membrane proximal external region of p15E. In order to analyse whether pigs are also able to produce such antibodies, and whether such antibodies can be used to study the involvement of the TM protein in placental development (as was shown for endogenous retroviruses of other species), German landrace pigs were immunized with PERV p15E. No binding and neutralizing antibodies were produced as shown in three Western blot analyses and in a neutralization assay, indicating that pigs are tolerant to their endogenous retroviruses, at least for the ectodomain of the TM protein.

NEAT1 Is a Novel Oncogenic LncRNA and Correlated with miR-143 in Pediatric Oligodendrogliomas

2021 ◽  
Vol 56 (2) ◽  
pp. 133-139
Author(s):  
Secil Ak Aksoy ◽  
Melis Mutlu ◽  
Rabia Nur Balcin ◽  
Mevlut Ozgur Taskapilioglu ◽  
Cagla Tekin ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Pediatric Brain Tumors ◽  
Normal Brain ◽  
Diffuse Glioma ◽  
Expression Levels ◽  
Treatment Models ◽  
New Treatment

Introduction: The noncoding RNAs (ncRNAs) play a role in biological processes of various cancers including gliomas. The majority of these transcripts are uniquely expressed in differentiated tissues or specific glioma types. Pediatric oligodendroglioma (POG) is a rare subtype of diffuse glioma and accounts for <1% of pediatric brain tumors. Because histologically POG resembles adult OG, the same treatment is applied as adults. However, the significance in predicting outcomes in POG patients is unclear. In this study, we aimed to investigate the prognostic significance of expression ­profiles of microRNA (miRNA) and long noncoding RNA ­(LncRNA) in POGs. Methods: We investigated the levels of 13 known miRNAs and 6 LncRNAs in tumor samples from 9 patients with primary POG by using RT-PCR and analyzed their association with outcomes. Results: The expression levels of miR-21, miR-106a, miR-10b, and LncRNA NEAT1 were higher, and the expression level of miR-143 was lower in POG tissues compared with normal brain tissues (p = 0.006, p = 0.032, p = 0.034, p = 0.002, and p = 0.001, respectively). High levels of NEAT1 and low expression of miR-143 were associated with decreased probability of short disease-free survival (p = 0.018 and p = 0.022, respectively). Discussion: NEAT1 and miR-143 levels could serve as reciprocal prognostic predictors of disease progression in patients with POG. New treatment models to regulate the expression levels of NEAT1 and miR-143 will bring a new approach to the therapy of POG.

scholarly journals The comparison of pro- and antioxidative parameters in plasma and placental tissues during early phase of placental development in cows

2021 ◽  
Author(s):  
Jacek Wawrzykowski ◽  
Monika Jamioł ◽  
Wioleta Mojsym ◽  
Marta Kankofer
Keyword(s):  
Blood Plasma ◽  
Antioxidative Enzymes ◽  
Placental Development ◽  
Blood Samples ◽  
Bovine Placenta ◽  
Total Antioxidant ◽  
Tissue Homogenates ◽  
Further Development ◽  
General Profile ◽  
In Blood Plasma

AbstractPhysiological balance between pro- and antioxidative processes is crucial for placentation and further development of fetus and placenta. Parameters of pro- and antioxidative profile may serve as markers of proper course of pregnancy. The aim of study was to assess whether the balance between pro- and antioxidative parameters during placentation phase in bovine placenta is maintained. Placental and blood samples were collected from healthy, HF, pregnant (2nd-3rd month) cows (n = 8) in slaughterhouse and in farm, respectively. Formylokinurenine and bityrosine content were measured spectrofluorimetrically in blood plasma and tissue homogenates while metabolites of lipid peroxidation, total antioxidant capacity, SH groups and activity of antioxidative enzymes (glutathione peroxidase and superoxide dismutase) were determined in examined tissues by spectrophotometry. Western blotting was used to confirm the presence of enzymatic proteins in placenta. Results: Local profile in tissues was more pronounced than general profile in blood plasma. Activities of antioxidative enzymes were significantly (p < 0.05) higher in 2nd compared to 3rd month of pregnancy in maternal part of placenta while prooxidant parameters showed opposite relationship. Obtained results showed significant differences when compared to data from non-pregnant animals or time of parturition. Further studies are necessary for elucidation of placentation phase in cows.

scholarly journals Pineal gland transcriptomic profiling reveals the differential regulation of lncRNA and mRNA related to prolificacy in STH sheep with two FecB genotypes

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Chunyan Li ◽  
Xiaoyun He ◽  
Zijun Zhang ◽  
Chunhuan Ren ◽  
Mingxing Chu
Keyword(s):  
Pineal Gland ◽  
Expression Pattern ◽  
Noncoding Rna ◽  
Target Genes ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Rna Seq ◽  
Important Regulator ◽  
Gsh Metabolism ◽  
Transcriptome Expression

Abstract Background Long noncoding RNA (lncRNA) has been identified as important regulator in hypothalamic-pituitary-ovarian axis associated with sheep prolificacy. However, little is known of their expression pattern and potential roles in the pineal gland of sheep. Herein, RNA-Seq was used to detect transcriptome expression pattern in pineal gland between follicular phase (FP) and luteal phase (LP) in FecBBB (MM) and FecB++ (ww) STH sheep, respectively, and differentially expressed (DE) lncRNAs and mRNAs associated with reproduction were identified. Results Overall, 135 DE lncRNAs and 1360 DE mRNAs in pineal gland between MM and ww sheep were screened. Wherein, 39 DE lncRNAs and 764 DE mRNAs were identified (FP vs LP) in MM sheep, 96 DE lncRNAs and 596 DE mRNAs were identified (FP vs LP) in ww sheep. Moreover, GO and KEGG enrichment analysis indicated that the targets of DE lncRNAs and DE mRNAs were annotated to multiple biological processes such as phototransduction, circadian rhythm, melanogenesis, GSH metabolism and steroid biosynthesis, which directly or indirectly participate in hormone activities to affect sheep reproductive performance. Additionally, co-expression of lncRNAs-mRNAs and the network construction were performed based on correlation analysis, DE lncRNAs can modulate target genes involved in related pathways to affect sheep fecundity. Specifically, XLOC_466330, XLOC_532771, XLOC_028449 targeting RRM2B and GSTK1, XLOC_391199 targeting STMN1, XLOC_503926 targeting RAG2, XLOC_187711 targeting DLG4 were included. Conclusion All of these differential lncRNAs and mRNAs expression profiles in pineal gland provide a novel resource for elucidating regulatory mechanism underlying STH sheep prolificacy.

scholarly journals Human Endogenous Retrovirus Reactivation: Implications for Cancer Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1999
Author(s):  
Annacarmen Petrizzo ◽  
Concetta Ragone ◽  
Beatrice Cavalluzzo ◽  
Angela Mauriello ◽  
Carmen Manolio ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Genetic Material ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retrovirus ◽  
Danger Signal ◽  
Human Endogenous Retroviruses ◽  
Double Stranded Rna ◽  
Specific Antigens ◽  
Viral Mimicry

Human endogenous retroviruses (HERVs) derive from ancestral exogenous retroviruses whose genetic material has been integrated in our germline DNA. Several lines of evidence indicate that cancer immunotherapy may benefit from HERV reactivation, which can be induced either by drugs or by cellular changes occurring in tumor cells. Indeed, several studies indicate that HERV proviral DNA can be transcribed either to double-stranded RNA (dsRNA) that is sensed as a “danger signal” by pattern recognition receptors (PRRs), leading to a viral mimicry state, or to mRNA that is translated into proteins that may contribute to the landscape of tumor-specific antigens (TSAs). Alternatively, HERV reactivation is associated with the expression of long noncoding RNAs (lncRNAs). In this review, we will highlight recent findings on HERV reactivation in cancer and its implications for cancer immunotherapy.

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