Identification of a small protein encoded by PCBP1-AS1 that promotes replication of influenza virus via inducing enhancement of autophagy
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ABSTRACT:
PROVIDER: PRJNA1064099 | ENA |
REPOSITORIES: ENA
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Project description:Many annotated long noncoding RNAs (lncRNAs) contain small open reading frames (sORFs), some of which have been demonstrated to encode small proteins or micropeptides with fundamental biological importance. However, the small proteins or micropeptides encoded by lncRNAs and their functions in viral infection remain largely unexplored. Here, we identified and characterized a small 110-amino acid protein named ORF6 encoded by the putative lncRNA PCBP1-AS1. Interestingly, both PCBP1-AS1 and ORF6 were significantly upregulated by influenza virus infection. Furthermore, we observed that they were markedly induced by type I interferon treatment. Overexpression of PCBP1-AS1 or ORF6 enhanced influenza virus replication. Conversely, knockdown of PCBP1-AS1 or knockout of ORF6 inhibited the viral production. In addition, loss-of-function experiment demonstrated that ORF6 is essential for PCBP1-AS1 to facilitate influenza virus replication. Importantly, the overexpression of ORF6 induced enhancement of autophagy by increasing the expression of ATG7, a gene encoding an essential effector enzyme for canonical autophagy. These findings reveal a lncRNA-derived small protein that is exploited by influenza virus, and provide new insights into the virus-host regulatory network.
2024-08-03 | GSE253139 | GEO
Project description:Many annotated long noncoding RNAs (lncRNAs) contain small open reading frames (sORFs), some of which have been demonstrated to encode small proteins or micropeptides with fundamental biological importance. While the small proteins or micropeptides hidden in lncRNA are gradually being revealed, their functions in influenza virus infection remain largely unexplored. Here, we identified and characterized a small 110-amino acid protein named PAESP that is encoded by the putative lncRNA PCBP1-AS1. We found that both PCBP1-AS1 and PAESP were upregulated by influenza virus infection as well as type I interferon treatment. Overexpression of PCBP1-AS1 or PAESP enhanced influenza virus replication. Conversely, knockdown of PCBP1-AS1 or knockout of PAESP inhibited viral production. In addition, loss-of-function experiment demonstrated that PAESP is essential for PCBP1-AS1 to facilitate influenza virus replication. More importantly, the overexpression of PAESP increases the mRNA level of several genes such as IFIT2 and IFIT3, which have been proved to be retasked by influenza virus from canonical antiviral factors into proviral effectors. Interestingly, when IFIT2 or IFIT3 expression was knocked down in PAESP-overexpressed cells, the virus titers significantly decreased compared to control cells. These findings reveal a novel lncRNA-derived small protein that is exploited by influenza virus and provide new insights into the virus-host regulatory network.
2024-08-03 | GSE252713 | GEO
Project description:Many annotated long noncoding RNAs (lncRNAs) contain small open reading frames (sORFs), some of which have been demonstrated to encode small proteins or micropeptides with fundamental biological importance. While the small proteins or micropeptides hidden in lncRNA are gradually being revealed, their functions in influenza virus infection remain largely unexplored. Here, we identified and characterized a small 110-amino acid protein named PAESP that is encoded by the putative lncRNA PCBP1-AS1. We found that both PCBP1-AS1 and PAESP were upregulated by influenza virus infection as well as type I interferon treatment. Overexpression of PCBP1-AS1 or PAESP enhanced influenza virus replication. Conversely, knockdown of PCBP1-AS1 or knockout of PAESP inhibited viral production. In addition, loss-of-function experiment demonstrated that PAESP is essential for PCBP1-AS1 to facilitate influenza virus replication. More importantly, the overexpression of PAESP increases the mRNA level of several genes such as IFIT2 and IFIT3, which have been proved to be retasked by influenza virus from canonical antiviral factors into proviral effectors. Interestingly, when IFIT2 or IFIT3 expression was knocked down in PAESP-overexpressed cells, the virus titers significantly decreased compared to control cells. These findings reveal a novel lncRNA-derived small protein that is exploited by influenza virus and provide new insights into the virus-host regulatory network.
2024-08-03 | GSE252920 | GEO
Project description:A small protein encoded by lncRNA PCBP1-AS1 promotes the replication of influenza virus via regulating the expression of proviral effectors
| PRJNA1062311 | ENA
Project description:RNA-binding proteins participate in a complex array of post-transcriptional controls essential to cell-type specification and somatic development. Despite their detailed biochemical characterizations, the degree to which each RNA-binding protein impacts on mammalian embryonic development remains incompletely defined and the level of functional redundancy among subsets of these proteins remains open to question. The poly-(C) binding proteins, Pcbp's (aCPs, hnRNPEs), are encoded by a highly conserved and broadly expressed gene family. The two major Pcbp isoforms, Pcbp2 and Pcbp1, are robustly expressed in a wide range of tissues and exert both nuclear and cytoplasmic controls over gene expression. Here we report that Pcbp1-null embryos are rendered nonviable in the peri-implantation stage. In contrast, Pcbp2-null embryos survive until mid-gestation at which time they undergo a loss in viability associated with cardiovascular and hematopoietic abnormalities. Adult mice heterozygous for either Pcbp1 or Pcbp2 null alleles display a mild and non-disruptive growth defect. These data reveal that Pcbp1 and Pcbp2 are individually essential for mouse embryonic development and post-natal growth, reveal a non-redundant in vivo role for Pcpb2 in hematopoiesis, and provide direct evidence that Pcbp1, a retrotransposed derivative of Pcpb2, has evolved essential function(s) in the mammalian genome. mRNA-seq on fetal liver tissue from 12.5 days post coitum. 4 replicates of WT and 3 replicates of PCBP2 Knockout
2015-11-05 | E-GEOD-72491 | biostudies-arrayexpress
Project description:A small protein encoded by lncRNA PCBP1-AS1 promotes the replication of influenza virus via regulating the expression of proviral effectors (Ribo-Seq)
| PRJNA1063244 | ENA
Project description:Iron deposition is frequently observed in human autoinflammatory diseases, such as in the brain of patients with multiple sclerosis or in the synovial fluid of patients with rheumatoid arthritis1-5. Yet, the functional outcome of excessive iron in inflammatory conditions is largely unknown. Granulocyte macrophage colony-stimulating factor (GM-CSF) is a proinflammatory cytokine promoting myeloid cell maturation and activation6 and is essential for the pathogenesis of many autoimmune diseases, including autoimmune encephalomyelitis7-10. Post-transcriptional regulation of GM-CSF is mediated primarily through its 3’ untranslated region (3’UTR) via interaction with specific RNA-binding proteins11. Here we show that a RNA-binding protein PCBP1 senses intracellular iron and post-transcriptionally promotes GM-CSF production. In a short hairpin (sh) RNA screening, we found that Poly(rC) binding protein 1 (PCBP1) enhanced GM-CSF 3’UTR activity and its endogenous mRNA stability. PCBP1 deficiency in autoreactive T cells resulted in a compromised production of GM-CSF and other proinflammatory cytokines, abolishing their capacity in inducing experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Using Crosslinking and Immunoprecipitation (CLIP)12, we demonstrated that PCBP1 promoted mRNA stability by recognizing CU rich elements in the 3’UTRs of pro-inflammatory cytokines. Furthermore, iron depletion induced rapid caspase-mediated proteolysis of PCBP1 and inhibited the production of GM-CSF and a module of 24 cytokines in primary murine and human T cells. Our study thus demonstrates that PCBP1 is critical for the post-transcriptional regulation of proinflammatory cytokines, and indicates that sensing iron may represent a simple yet effective means to adjust the inflammatory response to tissue homeostatic alterations.
2018-07-04 | GSE84699 | GEO
Project description:Iron deposition is frequently observed in human autoinflammatory diseases, such as in the brain of patients with multiple sclerosis or in the synovial fluid of patients with rheumatoid arthritis1-5. Yet, the functional outcome of excessive iron in inflammatory conditions is largely unknown. Granulocyte macrophage colony-stimulating factor (GM-CSF) is a proinflammatory cytokine promoting myeloid cell maturation and activation6 and is essential for the pathogenesis of many autoimmune diseases, including autoimmune encephalomyelitis7-10. Post-transcriptional regulation of GM-CSF is mediated primarily through its 3’ untranslated region (3’UTR) via interaction with specific RNA-binding proteins11. Here we show that a RNA-binding protein PCBP1 senses intracellular iron and post-transcriptionally promotes GM-CSF production. In a short hairpin (sh) RNA screening, we found that Poly(rC) binding protein 1 (PCBP1) enhanced GM-CSF 3’UTR activity and its endogenous mRNA stability. PCBP1 deficiency in autoreactive T cells resulted in a compromised production of GM-CSF and other proinflammatory cytokines, abolishing their capacity in inducing experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Using Crosslinking and Immunoprecipitation (CLIP)12, we demonstrated that PCBP1 promoted mRNA stability by recognizing CU rich elements in the 3’UTRs of pro-inflammatory cytokines. Furthermore, iron depletion induced rapid caspase-mediated proteolysis of PCBP1 and inhibited the production of GM-CSF and a module of 24 cytokines in primary murine and human T cells. Our study thus demonstrates that PCBP1 is critical for the post-transcriptional regulation of proinflammatory cytokines, and indicates that sensing iron may represent a simple yet effective means to adjust the inflammatory response to tissue homeostatic alterations.
2018-07-04 | GSE84700 | GEO
Project description:The aim of this study was to construct a lncRNA-mRNA co-expression function network and analyze lncRNAs that might contribute to the pathogenesis of cervical cancer. Transcriptome analysis of 3 cervical cancer samples and 3 adjacent tissue samples was completed in this project.LncRNA-mRNA correlation analysis, enrichment of functions, qPCR, K-M survival, clinicopathology analysis, GSEA and immune infiltration analysis were implemented. Total of 67.600 GB of Clean Data (sequencing Data after quality control) was obtained. The average amount of Clean Data of each sample was 11.267 GB, the percentage of Q30 base was above 91.18%, and the GC content was between 45.46% and 47.18%.Reference species: human;Reference genomic version: GRCH38;Reference genome source: http://asia.ensembl.org/Homo_sapiens/Info/Index;The sequencing data of each sample after quality control was compared with the specified reference genome, and the matching rates ranged from 95.957% to 97.270%, and the unique matching rates ranged from 91.363% to 94.258%. Transcriptomic and lncRNA-mRNA correlation analysis revealed PCBP1-AS1 plays a key role as an independent prognostic factor in patients with cervical cancer.
2021-02-24 | GSE167362 | GEO
Project description:RNA-binding proteins participate in a complex array of post-transcriptional controls essential to cell-type specification and somatic development. Despite their detailed biochemical characterizations, the degree to which each RNA-binding protein impacts on mammalian embryonic development remains incompletely defined and the level of functional redundancy among subsets of these proteins remains open to question. The poly-(C) binding proteins, Pcbp’s (aCPs, hnRNPEs), are encoded by a highly conserved and broadly expressed gene family. The two major Pcbp isoforms, Pcbp2 and Pcbp1, are robustly expressed in a wide range of tissues and exert both nuclear and cytoplasmic controls over gene expression. Here we report that Pcbp1-null embryos are rendered nonviable in the peri-implantation stage. In contrast, Pcbp2-null embryos survive until mid-gestation at which time they undergo a loss in viability associated with cardiovascular and hematopoietic abnormalities. Adult mice heterozygous for either Pcbp1 or Pcbp2 null alleles display a mild and non-disruptive growth defect. These data reveal that Pcbp1 and Pcbp2 are individually essential for mouse embryonic development and post-natal growth, reveal a non-redundant in vivo role for Pcpb2 in hematopoiesis, and provide direct evidence that Pcbp1, a retrotransposed derivative of Pcpb2, has evolved essential function(s) in the mammalian genome.
2015-11-05 | GSE72491 | GEO