Existence of human-virus chimeric proteins generated during infection
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ABSTRACT:
PROVIDER: PRJNA527980 | ENA |
REPOSITORIES: ENA
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2020-06-25 | GSE128519 | GEO
Project description:HUMAN-VIRUS CHIMERIC PROTEINS GENERATED DURING INFECTION
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Project description:RNA viruses are a major threat to global human health. The life cycles of many highly pathogenic RNA viruses like influenza A virus (IAV) and Lassa virus depends on host mRNA, as viral polymerases cleave 5′m7G-capped host transcripts to prime viral mRNA synthesis (‘cap-snatching’). We hypothesized that start codons within cap-snatched host transcripts could drive the expression of chimeric human-viral coding sequences. Here, we report the existence of this mechanism of gene origination (‘start-snatching’), which creates, depending on the translatability of the viral UTRs, human-virus protein chimeras either as N-terminally extended viral proteins or entirely novel polypeptides by genetic overprinting. We show that both types of chimeric proteins are made in IAV-infected cells, can generate T cell responses and contribute to virulence. Our results indicate that IAV, and likely a multitude of other human-, animal- and plant-viruses, use this host-dependent mechanism to expand their proteome diversity during infection.
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2020-08-31 | E-MTAB-8811 | biostudies-arrayexpress
Project description:We generated chimeric mice with livers that were predominantly repopulated with human hepatocytes. Hepatocytes were isolated from the chimeric mouse livers and their gene expressions were compared with hepatocytes isolated from normal human livers . Cluster and principal components analyses showed that gene expression profiles of hepatocytes from the chimeric mice and those from normal human livers were extremely closed. Additionally, we performed microarray experiments to examine gene expression in human tissues. This data was used for comparison with hepatocytes. A total of 22 tissues (bone marrow, cerebellum, colon, cortex, fetal brain, heart, kidney, liver, lung, pancreas, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testes, thymus, thyroid, trachea and uterus) were examined. The chimeric mice were generated by transplantation of 2 different donor hepatocytes. Hepatocytes were isolated from the mouse livers and normal human livers, and their cDNAs were used for microarray analysis. Total RNA isolated from human tissues and cell cultures were labeled and hybridized to the GeneChip Human Genome U133 Plus 2.0 Array according to the manufacturer's protocol.
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Project description:Ribosomal frameshifting refers to the process that ribosomes slip into +1 or -1 reading frame, thus produce chimeric trans-frame proteins. In viruses and bacteria, programmed ribosomal frameshifting can produce essential trans-frame proteins for viral replication or regulation of other biological processes. In humans, however, functional trans-frame protein derived from ribosomal frameshifting is scarcely documented. Combining multiple assays, we show that short codon repeats could act as cis-acting elements that stimulate ribosomal frameshifting in humans, abbreviated as CRFS hereafter. Using proteomic analyses, we identified many putative CRFS events from 32 normal human tissues supported by trans-frame peptides positioned at codon repeats. Finally, we show a CRFS-derived trans-frame protein (HDAC1-FS) functions by antagonizing the activities of HDAC1, thus affecting cell migration and apoptosis. These data suggest a novel type of translational recoding associated with codon repeats, which may expand the coding capacity of mRNA and diversify the regulation in human.
2023-05-01 | GSE220677 | GEO
Project description:Ribosomal frameshifting refers to the process that ribosomes slip into +1 or -1 reading frame, thus produce chimeric trans-frame proteins. In viruses and bacteria, programmed ribosomal frameshifting can produce essential trans-frame proteins for viral replication or regulation of other biological processes. In humans, however, functional trans-frame protein derived from ribosomal frameshifting is scarcely documented. Combining multiple assays, we show that short codon repeats could act as cis-acting elements that stimulate ribosomal frameshifting in humans, abbreviated as CRFS hereafter. Using proteomic analyses, we identified many putative CRFS events from 32 normal human tissues supported by trans-frame peptides positioned at codon repeats. Finally, we show a CRFS-derived trans-frame protein (HDAC1-FS) functions by antagonizing the activities of HDAC1, thus affecting cell migration and apoptosis. These data suggest a novel type of translational recoding associated with codon repeats,which may expand the coding capacity of mRNA and diversify the regulation in human.
2023-05-01 | GSE220676 | GEO