Circular RNAs Represent a Novel Class of Human Cytomegalovirus Transcripts
ABSTRACT Human cytomegalovirus (HCMV) infects a large portion of the human population globally. Several HCMV-derived noncoding RNAs are involved in the regulation of viral gene expression and the virus life cycle. Here, we reported that circRNAs are a new class of HCMV transcripts. We bioinformatica...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2022-06-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.01106-22 |
| _version_ | 1811333193572286464 |
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| author | Shaomin Yang Xiaolian Liu Mei Wang Di Cao Dabbu Kumar Jaijyan Nicole Enescu Jian Liu Songbin Wu Sashuang Wang Wuping Sun Lizu Xiao Alison Gu Yaolan Li Hong Zhou Sanjay Tyagi Jianguo Wu Qiyi Tang Hua Zhu |
| author_facet | Shaomin Yang Xiaolian Liu Mei Wang Di Cao Dabbu Kumar Jaijyan Nicole Enescu Jian Liu Songbin Wu Sashuang Wang Wuping Sun Lizu Xiao Alison Gu Yaolan Li Hong Zhou Sanjay Tyagi Jianguo Wu Qiyi Tang Hua Zhu |
| author_sort | Shaomin Yang |
| collection | DOAJ |
| description | ABSTRACT Human cytomegalovirus (HCMV) infects a large portion of the human population globally. Several HCMV-derived noncoding RNAs are involved in the regulation of viral gene expression and the virus life cycle. Here, we reported that circRNAs are a new class of HCMV transcripts. We bioinformatically predict 704 candidate circRNAs encoded by the TB40/E strain and 230 encoded by the HAN strain. We also systematically compare circRNA features, including the breakpoint sequence consensus, strand preference, length distribution, and exon numbers between host genome-encoded circRNAs and viral circRNAs, and showed that the unique characteristics of viral circRNAs are correlated with their genome types. Furthermore, we experimentally confirmed 324 back-splice junctions (BSJs) from three HCMV strains, Towne, TB40/E, and Toledo, and identified 4 representative HCMV circRNAs by RNase R treatment. Interestingly, we also showed that HCMV contains alternative back-splicing circRNAs. We developed a new amplified FISH method that allowed us to visualize circRNAs and quantify the number of circRNA molecules in the infected cells. The competitive endogenous RNA network analysis suggests that HCMV circRNAs play important roles in viral DNA synthesis via circRNA-miRNA-mRNA networks. Our findings highlight that circRNAs are an important component of the HCMV transcriptome that may contribute to viral replication and pathogenesis. IMPORTANCE HCMV infects 40% to 100% of the human population globally and may be a life-threatening pathogen in immunocompromised individuals. CircRNA is a family of unique RNA that is the most newly found and remains unknown in many aspects. Our current studies computationally identified HCMV-encoded circRNAs and confirmed the existence of the HCMV circRNAs in the infected cells. We systematically compared the features between host and different viral circRNAs and found that the unique characteristics of circRNAs were correlated with their genome types. We also first reported that HCMV contained alternative back-splicing circRNAs. More importantly, we developed a new amplified FISH method which allowed us for the first time not only to visualize circRNAs but also to quantify the number of circRNA molecules in the infected cells. This work describes a novel component of HCMV transcriptome bringing a new understanding of HCMV biology and disease. |
| first_indexed | 2024-04-13T16:48:28Z |
| format | Article |
| id | doaj.art-7e0bdef9ffba4424ae73d7c6ad87e447 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-04-13T16:48:28Z |
| publishDate | 2022-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-7e0bdef9ffba4424ae73d7c6ad87e4472022-12-22T02:39:00ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-06-0110310.1128/spectrum.01106-22Circular RNAs Represent a Novel Class of Human Cytomegalovirus TranscriptsShaomin Yang0Xiaolian Liu1Mei Wang2Di Cao3Dabbu Kumar Jaijyan4Nicole Enescu5Jian Liu6Songbin Wu7Sashuang Wang8Wuping Sun9Lizu Xiao10Alison Gu11Yaolan Li12Hong Zhou13Sanjay Tyagi14Jianguo Wu15Qiyi Tang16Hua Zhu17Jinan University, Guangzhou, Guangdong, ChinaJinan University, Guangzhou, Guangdong, ChinaJinan University, Guangzhou, Guangdong, ChinaJinan University, Guangzhou, Guangdong, ChinaDepartment of Microbiology and Molecular Genetics, New Jersey Medical School, Rutgers University, Newark, New Jersey, USADepartment of Microbiology and Molecular Genetics, New Jersey Medical School, Rutgers University, Newark, New Jersey, USASchool of Biological Sciences and Biotechnology, Minnan Normal University, Zhangzhou, Fujian, ChinaDepartment of Pain Medicine and Shenzhen Municipal Key Laboratory for Pain Medicine, Shenzhen Nanshan People's Hospital, The 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, ChinaDepartment of Pain Medicine and Shenzhen Municipal Key Laboratory for Pain Medicine, Shenzhen Nanshan People's Hospital, The 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, ChinaDepartment of Pain Medicine and Shenzhen Municipal Key Laboratory for Pain Medicine, Shenzhen Nanshan People's Hospital, The 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, ChinaDepartment of Pain Medicine and Shenzhen Municipal Key Laboratory for Pain Medicine, Shenzhen Nanshan People's Hospital, The 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, ChinaDepartment of Microbiology and Molecular Genetics, New Jersey Medical School, Rutgers University, Newark, New Jersey, USAJinan University, Guangzhou, Guangdong, ChinaDepartment of Microbiology, Howard University College of Medicine, Washington, DC, USAPublic Health Research Institute, New Jersey Medical School, Newark, New Jersey, USAJinan University, Guangzhou, Guangdong, ChinaDepartment of Microbiology, Howard University College of Medicine, Washington, DC, USADepartment of Microbiology and Molecular Genetics, New Jersey Medical School, Rutgers University, Newark, New Jersey, USAABSTRACT Human cytomegalovirus (HCMV) infects a large portion of the human population globally. Several HCMV-derived noncoding RNAs are involved in the regulation of viral gene expression and the virus life cycle. Here, we reported that circRNAs are a new class of HCMV transcripts. We bioinformatically predict 704 candidate circRNAs encoded by the TB40/E strain and 230 encoded by the HAN strain. We also systematically compare circRNA features, including the breakpoint sequence consensus, strand preference, length distribution, and exon numbers between host genome-encoded circRNAs and viral circRNAs, and showed that the unique characteristics of viral circRNAs are correlated with their genome types. Furthermore, we experimentally confirmed 324 back-splice junctions (BSJs) from three HCMV strains, Towne, TB40/E, and Toledo, and identified 4 representative HCMV circRNAs by RNase R treatment. Interestingly, we also showed that HCMV contains alternative back-splicing circRNAs. We developed a new amplified FISH method that allowed us to visualize circRNAs and quantify the number of circRNA molecules in the infected cells. The competitive endogenous RNA network analysis suggests that HCMV circRNAs play important roles in viral DNA synthesis via circRNA-miRNA-mRNA networks. Our findings highlight that circRNAs are an important component of the HCMV transcriptome that may contribute to viral replication and pathogenesis. IMPORTANCE HCMV infects 40% to 100% of the human population globally and may be a life-threatening pathogen in immunocompromised individuals. CircRNA is a family of unique RNA that is the most newly found and remains unknown in many aspects. Our current studies computationally identified HCMV-encoded circRNAs and confirmed the existence of the HCMV circRNAs in the infected cells. We systematically compared the features between host and different viral circRNAs and found that the unique characteristics of circRNAs were correlated with their genome types. We also first reported that HCMV contained alternative back-splicing circRNAs. More importantly, we developed a new amplified FISH method which allowed us for the first time not only to visualize circRNAs but also to quantify the number of circRNA molecules in the infected cells. This work describes a novel component of HCMV transcriptome bringing a new understanding of HCMV biology and disease.https://journals.asm.org/doi/10.1128/spectrum.01106-22cytomegalovirusHCMVEBVKSHVcircRNARNA splice junction |
| spellingShingle | Shaomin Yang Xiaolian Liu Mei Wang Di Cao Dabbu Kumar Jaijyan Nicole Enescu Jian Liu Songbin Wu Sashuang Wang Wuping Sun Lizu Xiao Alison Gu Yaolan Li Hong Zhou Sanjay Tyagi Jianguo Wu Qiyi Tang Hua Zhu Circular RNAs Represent a Novel Class of Human Cytomegalovirus Transcripts Microbiology Spectrum cytomegalovirus HCMV EBV KSHV circRNA RNA splice junction |
| title | Circular RNAs Represent a Novel Class of Human Cytomegalovirus Transcripts |
| title_full | Circular RNAs Represent a Novel Class of Human Cytomegalovirus Transcripts |
| title_fullStr | Circular RNAs Represent a Novel Class of Human Cytomegalovirus Transcripts |
| title_full_unstemmed | Circular RNAs Represent a Novel Class of Human Cytomegalovirus Transcripts |
| title_short | Circular RNAs Represent a Novel Class of Human Cytomegalovirus Transcripts |
| title_sort | circular rnas represent a novel class of human cytomegalovirus transcripts |
| topic | cytomegalovirus HCMV EBV KSHV circRNA RNA splice junction |
| url | https://journals.asm.org/doi/10.1128/spectrum.01106-22 |
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