Tumor Virus RNA Biology Section

Zhi-Ming Zheng, M.D., Ph.D.


A torn paper highlights that all four RNA isoforms of SRSF3, mapped by RNA-seq reads-distribution and illustrated by the Integrative Genomics Viewer, have a much shorter 3’ UTR from the annotated SRSF3 gene in yellow color (See the research article by Yu, et al. in this issue).

Revisiting and corrections to the annotated SRSF3 (SRp20) gene structure and RefSeq sequences from the human and mouse genomes

Published Date

SRSF3 (SRp20) is the smallest member of the serine/arginine (SR)-rich protein family. We found the annotated human SRSF3 and mouse Srsf3 RefSeq sequences are much larger than the detected SRSF3/Srsf3 RNA size by Northern blot. Mapping of RNA-seq reads from various human and mouse cell lines to the annotated SRSF3/Srsf3 gene illustrated only a partial coverage of its terminal exon 7. By 5ʹ RACE and 3ʹ RACE, we determined that SRSF3 gene spanning over 8422 bases and Srsf3 gene spanning over 9423 bases. SRSF3/Srsf3 gene has seven exons with exon 7 bearing two alternative polyadenylation signals (PAS). Through alternative PAS selection and exon 4 exclusion/inclusion by alternative RNA splicing, SRSF3/Srsf3 gene expresses four RNA isoforms. The major SRSF3 mRNA isoform with exon 4 exclusion by using a favorable distal PAS to encode a full-length protein is 1411 nt long (not annotated 4228 nt) and the same major mouse Srsf3 mRNA isoform is only 1295 nt (not annotated 2585 nt). The difference from the redefined RNA size of SRSF3/Srsf3 to the corresponding RefSeq sequence is at the 3’ UTR region. Collectively, the redefined SRSF3/Srsf3 gene structure and expression will allow better understanding of SRSF3 functions and its regulations in health and diseases.


Lulu Yu, Vladimir Majerciak, Rong Jia, Zhi-MIng Zheng, Revisiting and corrections to the annotated SRSF3 (SRp20) gene structure and RefSeq sequences from the human and mouse genomes. Cell Insight 2 (2): e100089, 2023.

Virologica Sinica cover April 2019

Towards Better Understanding of KSHV Life Cycle: from Transcription and Posttranscriptional Regulations to Pathogenesis 2) HPV18 Utilizes Two Alternative Branch Sites for E6*I Splicing to Produce E7 Protein

Published Date

1) Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8 (HHV-8), is etiologically linked to the development of Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. In this review, Yan and Majerciak et al. summarize the current research status on the biology of latent and lytic viral infection, the regulation of viral life cycles and the related pathogenesis.

2) Human papillomavirus 18 (HPV18) E6 and E7 oncogenes are transcribed as a single bicistronic E6E7 pre-mRNA. The E6 ORF region in the bicistronic E6E7 pre-mRNA contains an intron. Splicing of this intron disrupts the E6 ORF integrity and produces a spliced E6*I RNA for efficient E7 translation. Brant et al. identified two alternative branch sites in the HPV18 E6 intron which selection correlates to the efficiency of E6*I splicing and the production of E6 and E7 oncoproteins during productive or oncogenic HPV infection.


1) Lijun Yan, Vladimir Majerciak, Zhi-Ming Zheng, Ke Lan. Towards Better Understanding of KSHV Life Cycle: from Transcription and Posttranscriptional Regulations to Pathogenesis. Virologica Sinica 34 (2):135–161, 2019.

2) Ayslan Castro Brant, Vladimir Majerciak, Miguel Angelo Martins Moreira, Zhi-Ming Zheng. HPV18 Utilizes Two Alternative Branch Sites for E6*I Splicing to Produce E7 Protein. Virologica Sinica 34 (2): 211–221, 2019.

International Journal of Biological Sciences cover November 2015

Adapted Resistance to the Knockdown Effect of shRNA-Derived Srsf3 siRNAs in Mouse Littermates

Published Date

Gene silencing techniques are widely used to control gene expression and have potential for RNAi-based therapeutics. In this report, transgenic mouse lines were created for conditional knockdown of Srsf3 (SRp20) expression in liver and mammary gland tissues by expressing Srsf3-specific shRNAs driven by a U6 promoter. Although a small portion of the transgenic mouse littermates were found to produce siRNAs in the targeted tissues, most of the transgenic littermates at two months of age failed to display a knockdown phenotype of Srsf3 expression in their liver and mammary gland tissues where an abundant level of Srsf3 siRNAs remained. We saw only one of four mice with liver/mammary gland expressing Srsf3 siRNA displayed a suppressed level of Srsf3 protein, but not the mRNA. Data indicate that the host resistance to a gene-specific siRNA targeting an essential gene transcript can be developed in animals, presumably as a physiological necessity to cope with the hostile perturbation.


Ajiro M, Jia R, Wang RH, Deng CX, Zheng ZM. Adapted Resistance to the Knockdown Effect of shRNA-Derived Srsf3 siRNAs in Mouse Littermates. Int J Biol Sci 11(11):1248-1256, 2015. doi:10.7150/ijbs.13011

Kaposi's Sarcoma-Associated Herpesvirus book cover September 2015

Kaposi's Sarcoma-Associated Herpesvirus

Published Date

The discovery of KSHV in 1994 was a historical landmark in tumor virology and human cancer research. KSHV's subsequent identification as a cause of Kaposi sarcoma and its association with primary effusion lymphoma and multicentric Castleman disease soon attracted the attention of hundreds of research laboratories and motivated thousands of virologists and oncologists to switch their research directions. To date, PubMed has collected nearly 5000 papers on KSHV from numerous journal publications throughout the world. These studies indicate that the global fight against human cancers will continue to receive great support from our tremendous efforts in searching for new tumor-causing viruses and in understanding the basic biology of tumor viruses. To celebrate the 20th year of KSHV's discovery, I am very proud to be an invited Guest Editor for a Special Issue on KSHV in Viruses and am happy to assemble all published articles from the Special Issue into this book, Kaposi Sarcoma Associated Herpesvirus.


This book is a reprint of the special issue that appeared in the online open access journal Viruses (ISSN 1999-4915) in 2014.

Job Vacancies

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Postdoctoral Fellow - Tumor Viruses, RNA Biology Ph.D. or equivalent, M.D. or equivalent Zhi-Ming Zheng, M.D., Ph.D.


Xuefeng Liu
Dr. Xuefeng Liu
Professor, Department of Pathology, OSU School of Medicine
Shuang Tang
Dr. Shuang Tang
Senior Staff, U.S. Food and Drug Administration
Sohrab Bodaghi
Dr. Sohrab Bodaghi
Research Associate, University of California, Riverside
Lifang Zhang
Dr. Lifang Zhang
Professor and Chair, Department of Microbiology and Immunology, Wenzhou Medical University, China
Mingfang Tao
Dr. Mingfang Tao
Research Associate, Case Western Reserve University
Koji Yamanegi
Dr. Koji Yamanegi
Associate Professor, Department of Pathology, Hyogo College of Medicine, Japan
Rong Jia
Dr. Rong Jia
Professor and Deputy Director, Wuhan University School of Stomatology, China
Natalia Pripuzova
Dr. Natalia Pripuzova
Head, International Regulatory Group, R-Pharm, Moscow
Xiaohong Wang
Dr. Xiaohong Wang
Biotechnology Analyst Senior Advisor, General Dynamics Information Technology, Frederick, MD
Jeong-Gu Kang
Dr. Jeong-Gu Kang
President and Chief Executive Officer of NeuroBo Pharmaceuticals, Boston
Maria Julia Massimelli
Dr. Maria Julia Massimelli
Associate Professor, Maastricht University, The Netherlands
Masihiko Ajiro
Dr. Masihiko Ajiro
Assistant Professor, Kyoto University, Japan
Yang Li
Dr. Yang Li
Associate Professor, Zhejiang University Women's Hospital, China
Xiaofan Li
Dr. Xiaofan Li
Research Fellow, National Cancer Institute, NIH
Nishi Sharma
Dr. Nishi Sharma
Assistant Professor, Jamia Hamdard University, Delhi, India
Yanping Ma
Dr. Yanping Ma
Professor, Virology Laboratory, China Medical University, Shengyang, China
Junfen Xu
Dr. Junfen Xu
Associate Professor, Zhejiang University Women's Hospital, China
Xiang-Yang Xue
Dr. Xiang-Yang Xue
Professor and Associate Dean, Wenzhou Medical University, China
Tingting Zhang
Dr. Tingting Zhang
Associate Professor, Tianjin Medical University Dental School, China
Andrew Beltcappellino
Mr. Andrew Beltcappellino
Graduate Student, Columbia University
Pengfei Jiang
Dr. Pengfei Jiang
Associate Professor, Wenzhou Medical University, China
Mina Griffoen
Ms. Mina Griffoen
Ph.D. Student, University of Colorado
Haibin Liu
Dr. Haibin Liu
Assoc. Prof., Wuhan Institute of Virology, CAS
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Dr. Shivalee Duduskar
Postdoctoral Fellow (Visiting) NCI-DRP
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Dr. Sukkum Chang
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Dr. Beatriz Alvarado Hernandez


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