SYNCRIP facilitates porcine parvovirus viral DNA replication through the alternative splicing of NS1 mRNA to promote NS2 mRNA formation
Abstract Porcine Parvovirus (PPV), a pathogen causing porcine reproductive disorders, encodes two capsid proteins (VP1 and VP2) and three nonstructural proteins (NS1, NS2 and SAT) in infected cells. The PPV NS2 mRNA is from NS1 mRNA after alternative splicing, yet the corresponding mechanism is uncl...
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BMC
2021-05-01
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Online Access: | https://doi.org/10.1186/s13567-021-00938-6 |
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author | Songbiao Chen Bichen Miao Nannan Chen Caiyi Chen Ting Shao Xuezhi Zhang Lingling Chang Xiujuan Zhang Qian Du Yong Huang Dewen Tong |
author_facet | Songbiao Chen Bichen Miao Nannan Chen Caiyi Chen Ting Shao Xuezhi Zhang Lingling Chang Xiujuan Zhang Qian Du Yong Huang Dewen Tong |
author_sort | Songbiao Chen |
collection | DOAJ |
description | Abstract Porcine Parvovirus (PPV), a pathogen causing porcine reproductive disorders, encodes two capsid proteins (VP1 and VP2) and three nonstructural proteins (NS1, NS2 and SAT) in infected cells. The PPV NS2 mRNA is from NS1 mRNA after alternative splicing, yet the corresponding mechanism is unclear. In this study, we identified a PPV NS1 mRNA binding protein SYNCRIP, which belongs to the hnRNP family and has been identified to be involved in host pre-mRNA splicing by RNA-pulldown and mass spectrometry approaches. SYNCRIP was found to be significantly up-regulated by PPV infection in vivo and in vitro. We confirmed that it directly interacts with PPV NS1 mRNA and is co-localized at the cytoplasm in PPV-infected cells. Overexpression of SYNCRIP significantly reduced the NS1 mRNA and protein levels, whereas deletion of SYNCRIP significantly reduced NS2 mRNA and protein levels and the ratio of NS2 to NS1, and further impaired replication of the PPV. Furthermore, we found that SYNCRIP was able to bind the 3′-terminal site of NS1 mRNA to promote the cleavage of NS1 mRNA into NS2 mRNA. Taken together, the results presented here demonstrate that SYNCRIP is a critical molecule in the alternative splicing process of PPV mRNA, while revealing a novel function for this protein and providing a potential target of antiviral intervention for the control of porcine parvovirus disease. |
first_indexed | 2024-12-17T21:35:26Z |
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issn | 1297-9716 |
language | English |
last_indexed | 2024-12-17T21:35:26Z |
publishDate | 2021-05-01 |
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series | Veterinary Research |
spelling | doaj.art-5595503379314890a2b61cdce9ff4abd2022-12-21T21:31:46ZengBMCVeterinary Research1297-97162021-05-0152111510.1186/s13567-021-00938-6SYNCRIP facilitates porcine parvovirus viral DNA replication through the alternative splicing of NS1 mRNA to promote NS2 mRNA formationSongbiao Chen0Bichen Miao1Nannan Chen2Caiyi Chen3Ting Shao4Xuezhi Zhang5Lingling Chang6Xiujuan Zhang7Qian Du8Yong Huang9Dewen Tong10College of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityAbstract Porcine Parvovirus (PPV), a pathogen causing porcine reproductive disorders, encodes two capsid proteins (VP1 and VP2) and three nonstructural proteins (NS1, NS2 and SAT) in infected cells. The PPV NS2 mRNA is from NS1 mRNA after alternative splicing, yet the corresponding mechanism is unclear. In this study, we identified a PPV NS1 mRNA binding protein SYNCRIP, which belongs to the hnRNP family and has been identified to be involved in host pre-mRNA splicing by RNA-pulldown and mass spectrometry approaches. SYNCRIP was found to be significantly up-regulated by PPV infection in vivo and in vitro. We confirmed that it directly interacts with PPV NS1 mRNA and is co-localized at the cytoplasm in PPV-infected cells. Overexpression of SYNCRIP significantly reduced the NS1 mRNA and protein levels, whereas deletion of SYNCRIP significantly reduced NS2 mRNA and protein levels and the ratio of NS2 to NS1, and further impaired replication of the PPV. Furthermore, we found that SYNCRIP was able to bind the 3′-terminal site of NS1 mRNA to promote the cleavage of NS1 mRNA into NS2 mRNA. Taken together, the results presented here demonstrate that SYNCRIP is a critical molecule in the alternative splicing process of PPV mRNA, while revealing a novel function for this protein and providing a potential target of antiviral intervention for the control of porcine parvovirus disease.https://doi.org/10.1186/s13567-021-00938-6PPVSYNCRIPNS1 mRNAAlternative splicingNS2 mRNA |
spellingShingle | Songbiao Chen Bichen Miao Nannan Chen Caiyi Chen Ting Shao Xuezhi Zhang Lingling Chang Xiujuan Zhang Qian Du Yong Huang Dewen Tong SYNCRIP facilitates porcine parvovirus viral DNA replication through the alternative splicing of NS1 mRNA to promote NS2 mRNA formation Veterinary Research PPV SYNCRIP NS1 mRNA Alternative splicing NS2 mRNA |
title | SYNCRIP facilitates porcine parvovirus viral DNA replication through the alternative splicing of NS1 mRNA to promote NS2 mRNA formation |
title_full | SYNCRIP facilitates porcine parvovirus viral DNA replication through the alternative splicing of NS1 mRNA to promote NS2 mRNA formation |
title_fullStr | SYNCRIP facilitates porcine parvovirus viral DNA replication through the alternative splicing of NS1 mRNA to promote NS2 mRNA formation |
title_full_unstemmed | SYNCRIP facilitates porcine parvovirus viral DNA replication through the alternative splicing of NS1 mRNA to promote NS2 mRNA formation |
title_short | SYNCRIP facilitates porcine parvovirus viral DNA replication through the alternative splicing of NS1 mRNA to promote NS2 mRNA formation |
title_sort | syncrip facilitates porcine parvovirus viral dna replication through the alternative splicing of ns1 mrna to promote ns2 mrna formation |
topic | PPV SYNCRIP NS1 mRNA Alternative splicing NS2 mRNA |
url | https://doi.org/10.1186/s13567-021-00938-6 |
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