Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA85223 | ENA |
REPOSITORIES: ENA
Similar Datasets
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Project description:Human Cytomegalovirus Infection Causes Premature and Abnormal Differentiation of Human Neural Progenitor Cells
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Project description:Human cytomegalovirus (HCMV) is a prevalent pathogen that chronically infects the majority of human population. Among the many features that allow such widespread HCMV infection, one is its ability to maintain a transcriptionally dormant immune-evasive state called latency by suppressing its own major immediate early promoter (MIEP) via epigenetic alterations. In this study, we show a novel mechanism of MIEP regulation in which the major immediate early (MIE) gene product, IE1, downregulates its own promoter activity in an m6A modification-dependent manner. We found that the loss of the m6A writer, METTL3, in host cell results in the failure of HCMV to establish latency in these cells. Through transcriptome-wide m6A profiling of latently infected monocytes, we identified that the major immediate early gene product IE1 is m6A-modified during latent infection, with an m6A profile that is distinct from that found during lytic infection. Using an IE1-specific m6A-abolished mutant, we found that latent infection-specific m6A modification of the IE1 transcript was necessary for the efficient repression of MIEP, and this mutant virus failed to establish latency and progressed toward lytic-like infection in THP-1 cells. Our findings demonstrate that HCMV exploits the host m6A machinery to suppress its own lytic program to establish latency and uncover an unexpected role of immediate early gene mRNA in regulating its own expression.
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Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs. One-condition experment, gene expression of 3A6
2010-09-25 | E-GEOD-24338 | biostudies-arrayexpress
Project description:We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3’ and/or 5’ end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5’ differences and in support of this we report that a 5’ isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5’ isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes
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