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Status |
Public on Dec 07, 2020 |
Title |
Merkel Cell Polyomavirus Encodes Circular RNAs (circRNAs) Enabling a Dynamic circRNA/microRNA/mRNA Regulatory Network |
Organisms |
Homo sapiens; Rattus norvegicus |
Experiment type |
Other
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Summary |
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.
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Overall design |
Ribodepleted RNaseR treated total RNA from MCV positive MCC derived cell lines, RatPyV2 positve rat parotid tissue or 293 cell transfected with a recircularized MCV-HF genome was used for RNA sequencing
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Contributor(s) |
Abere B, Chang Y |
Citation(s) |
33323517 |
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Submission date |
Dec 03, 2020 |
Last update date |
Jan 11, 2021 |
Contact name |
Bizunesh Abere |
E-mail(s) |
baa103@pitt.edu
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Phone |
4126237733
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Organization name |
Hillman Cancer Center
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Department |
Cancer Virology Program
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Lab |
Chang and Moore
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Street address |
5117 Centre Ave, Research Pav. Suite 1.8
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City |
Pittsburgh |
State/province |
PENNSYLVANIA |
ZIP/Postal code |
15213 |
Country |
USA |
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Platforms (2) |
GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
GPL22396 |
Illumina HiSeq 4000 (Rattus norvegicus) |
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Samples (4)
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Relations |
BioProject |
PRJNA682427 |
SRA |
SRP295705 |
Supplementary file |
Size |
Download |
File type/resource |
GSE162627_RAW.tar |
10.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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