Merkel Cell Polyomavirus Encodes Circular RNAs (circRNAs) Enabling a Dynamic circRNA/microRNA/mRNA Regulatory Network
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA682427 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13194213_1.fastq.gz | Fastqsanger.gz | |||
| SRR13194213_2.fastq.gz | Fastqsanger.gz | |||
| SRR13194214_1.fastq.gz | Fastqsanger.gz | |||
| SRR13194214_2.fastq.gz | Fastqsanger.gz | |||
| SRR13194215_1.fastq.gz | Fastqsanger.gz |
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Project description:Viral noncoding RNAs have acquired increasing prominence as important regulators of infection and mediators of pathogenesis. Circular RNAs (circRNAs) generated by backsplicing events have been identified in several oncogenic human DNA viruses. Here, we show that Merkel cell polyomavirus (MCV), the etiologic cause of ~80% of Merkel cell carcinomas (MCCs), also expresses circular RNAs. By RNase R-resistant RNA sequencing, four putative circRNA backsplice junctions (BSJs) were identified from the MCV early region (ER). The most abundantly expressed MCV circRNA, designated circMCVT, is generated through backsplicing of all of ER exon II to form a 762-nucleotide (nt) circular RNA molecule. Curiously, circMCV-T, as well as two other less abundantly expressed putative MCV circRNAs, overlaps in a complementary fashion the MCV microRNA (miRNA) locus that encodes MCV-miR-M1. circMCV-T is consistently detected in concert with linear T antigen transcripts throughout infection, suggesting a crucial role for this RNA molecule in the regulatory functions of the early region, known to be vital for viral replication. Knocking out the hairpin structure of MCV-miR-M1 in genomic early region expression constructs and using a new high-efficiency, recombinase-mediated, recircularized MCV molecular clone demonstrates that circMCV-T levels decrease in the presence of MCV-miR-M1, underscoring the interplay between MCV circRNA and miRNA. Furthermore, circMCV-T partially reverses the known inhibitory effect of MCV-miR-M1 on early gene expression. RNase R-resistant RNA sequencing of lytic rat polyomavirus 2 (RatPyV2) identified an analogously located circRNA, stipulating a crucial, conserved regulatory function of this class of RNA molecules in the family of polyomaviruses.
2020-12-07 | GSE162627 | GEO
Project description:Merkel cells are epidermal mechanoreceptor cells responsible for the perception of gentle touch. Merkel cell carcinoma (MCC) is a rare and highly aggressive skin cancer. Although MCC histologically resembles Merkel cells, the cell of origin for MCC is unknown. MCC frequently contains integrated Merkel cell polyomavirus (MCPyV), a small DNA tumor virus with widespread prevalence. Whether MCPyV can transform Merkel cells is unknown. Here, we describe the isolation and long-term expansion of human Merkel cells from neonatal foreskin. We validated the expression of several Merkel cell-related factors by RNASeq, and assessed the ultrastructure by electron microscopy. Culture of Merkel cell preparations on an artificial basement membrane promoted the formation of structures containing both Merkel and non-Merkel cell populations. To determine whether Merkel cells were susceptible to transformation, we expressed tumor-derived MCPyV T antigens and additional oncogenes. We were unable to demonstrate tumorigenesis in immunodeficient mice, but were able to detect T antigen expression from excised cells weeks after implantation. These results highlight that foreskin-isolated Merkel cells can be propagated extensively, sustain expression of MCPyV T antigens, but are not susceptible to transformation by MCPyV, suggesting that Merkel cells from non-glabrous skin may not be a cell of origin for MCC.
2017-04-01 | GSE79657 | GEO
Project description:Viral noncoding RNAs have acquired increasing prominence as important regulators of infection and mediators of pathogenesis. Circular RNAs (circRNAs) generated by backsplicing events have been identified in several oncogenic human DNA viruses. Here, we show that Merkel cell polyomavirus (MCV), the etiologic cause of ?80% of Merkel cell carcinomas (MCCs), also expresses circular RNAs. By RNase R-resistant RNA sequencing, four putative circRNA backsplice junctions (BSJs) were identified from the MCV early region (ER). The most abundantly expressed MCV circRNA, designated circMCV-T, is generated through backsplicing of all of ER exon II to form a 762-nucleotide (nt) circular RNA molecule. Curiously, circMCV-T, as well as two other less abundantly expressed putative MCV circRNAs, overlaps in a complementary fashion with the MCV microRNA (miRNA) locus that encodes MCV-miR-M1. circMCV-T is consistently detected in concert with linear T antigen transcripts throughout infection, suggesting a crucial role for this RNA molecule in the regulatory functions of the early region, known to be vital for viral replication. Knocking out the hairpin structure of MCV-miR-M1 in genomic early region expression constructs and using a new high-efficiency, recombinase-mediated, recircularized MCV molecular clone demonstrates that circMCV-T levels decrease in the presence of MCV-miR-M1, underscoring the interplay between MCV circRNA and miRNA. Furthermore, circMCV-T partially reverses the known inhibitory effect of MCV-miR-M1 on early gene expression. RNase R-resistant RNA sequencing of lytic rat polyomavirus 2 (RatPyV2) identified an analogously located circRNA, stipulating a crucial, conserved regulatory function of this class of RNA molecules in the family of polyomaviruses.IMPORTANCE Covalently closed circular RNAs were recently described in the human DNA tumor viruses Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and human papillomavirus (HPV). Here, we show that MCV, another DNA tumor virus, generates circRNAs from its early regulatory region in concert with T antigen linear transcripts. MCV circMCV-T interacts with another MCV noncoding RNA, miR-M1, to functionally modulate early region transcript expression important for viral replication and long-term episomal persistence. This work describes a dynamic regulatory network integrating circRNA/miRNA/mRNA biomolecules and underscores the intricate functional modulation between several classes of polyomavirus-encoded RNAs in the control of viral replication.
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Project description:Merkel cell polyomavirus (MCPyV) small tumor antigen (ST), truncated large tumor antigen (TLT), early region (ER), and GFP control inducible vectors were introduced into IMR90 human lung embryonic fibrobrasts. After induction, cells were extracted and sequenced in triplicate every 4 hours for the first 24 hours, then every 8 hours until 48 hours. The purpose of this experiment was to identify the dynamic host response to MCPyV oncogenes, using both differential expression analysis and transcriptional network reconstruction, and to provide a systems-level understanding of the initial steps toward Merkel cell carcinoma.
2023-11-06 | GSE130639 | GEO
Project description:Merkel cell carcinoma is supposed to be derived from Merkel cells after infection by Merkel cell polyomavirus (MCV) and other poorly known events. A transcriptional profiling with cDNA microarrays was performed on cells from MCV+ Merkel cell carcinomas and isolated normal Merkel cells. This microarray revealed numerous significantly upregulated genes and down-regulated genes. The extensive list of genes identified in these experiments provides a large body of potentially valuable information of Merkel cell carcinoma carcinogenesis and could represent a source of potential targets for cancer therapy. Two-conditions experiment, MCV vs Normal Merkel Cell. Biological replicates : 4 MCV (Cy5), 1 control = pool of Normal Merkel cells from 3 liftings
2014-01-01 | E-GEOD-50434 | biostudies-arrayexpress
Project description:Merkel cell polyomavirus (MCPyV) early region (ER) and vector control inducible vectors were introduced into neonatal human dermal fibroblasts (nHDFs). Total RNA was then extracted and sequenced in triplicate at 0, 48 and 96 hours post-induction with doxycycline treatment. The purpose of this experiment was to identify the host response to MCPyV ER at the transcriptomic level, using both differential expression analysis and transcriptional network reconstruction. Together with our previous IMR90 model, we aim to systematically understand the initial steps toward Merkel cell carcinoma in different potential precursor cell types.
2024-12-16 | GSE278335 | GEO
Project description:Merkel cell polyomavirus (MCV) is clonally integrated in over 80% of Merkel cell carcinomas and mediates tumor development through the expression of viral oncoproteins large T (LT) and small T antigens (sT). Viral integration is associated with signature mutations in the T antigen locus that result in deletions of carboxy-terminal replicative functions of the LT antigen. Despite these truncations, the LT LxCxE retinoblastoma (Rb) pocket protein family-binding domain is retained, and the entire sT isoform is maintained intact. To investigate the ability of MCV oncoproteins to regulate host gene expression, we performed microarray analysis on cells stably expressing tumor-derived LT, tumor-derived LT along with sT, and tumor-derived LT with a mutated Rb interaction motif. Gene expression alterations in the presence of tumor-derived LT could be classified into three main groups: genes that are involved in the cell cycle (specifically the G1/S transition), genes involved in DNA replication, and genes involved in cellular movement. The LxCxE mutant LT largely reversed gene expression alterations detected with the wild type LT, while co-expression of sT did not significantly affect these patterns of gene expression. LxCxE-dependent upregulation of cyclin E and CDK2 correlates with increased proliferation in tumor-derived LT expressing cells. We conclude that in hTERT-immortalized human fibroblasts the LXCXE motif of tumor-derived LT enhances cellular proliferation and upregulates cell cycle and immune signaling gene transcription. RNA was isolated from BJ-hTERT cell lines and hybridized to an Illumina chip for global gene expression analysis
2015-09-21 | E-GEOD-68503 | biostudies-arrayexpress
Project description:Merkel cell polyomavirus (MCPyV) is linked to Merkel cell carcinoma (MCC), a rare and aggressive skin cancer. This study investigated the influence of MCPyV T antigens on the host genome using transcriptomics and epigenomics. Results revealed a role for the small Tumor (sT) antigen in subverting type I interferon response and immune evasion, contributing to persistent infection and tumor progression. These findings enhance our understanding of MCPyV pathogenesis and may inform new therapeutic strategies.
2024-04-04 | GSE230758 | GEO
Project description:Merkel cell polyomavirus (MCPyV) is linked to Merkel cell carcinoma (MCC), a rare and aggressive skin cancer. This study investigated the influence of MCPyV T antigens on the host genome using transcriptomics and epigenomics. Results revealed a role for the small Tumor (sT) antigen in subverting type I interferon response and immune evasion, contributing to persistent infection and tumor progression. These findings enhance our understanding of MCPyV pathogenesis and may inform new therapeutic strategies.
2024-04-04 | GSE229019 | GEO
Project description:Merkel cell carcinoma is supposed to be derived from Merkel cells after infection by Merkel cell polyomavirus (MCPyV) and other poorly known events. A transcriptional profiling with cDNA microarrays was performed on cells from MCPyV(+) Merkel cell carcinomas and isolated normal Merkel cells. This microarray revealed numerous significantly upregulated genes and downregulated genes. The extensive list of genes identified in these experiments provides a large body of potentially valuable information of Merkel cell carcinoma carcinogenesis and could represent a source of potential targets for cancer therapy.
2014-01-01 | GSE50434 | GEO