Journal article
N6-methyladenosine modification of a parvovirus-encoded small noncoding RNA facilitates viral DNA replication through recruiting Y-family DNA polymerases
Proceedings of the National Academy of Sciences - PNAS, Vol.121(25), e2320782121
06/18/2024
DOI: 10.1073/pnas.2320782121
PMCID: PMC11194592
PMID: 38875150
Abstract
Human bocavirus 1 (HBoV1) is a human parvovirus that causes lower respiratory tract infections in young children. It contains a single-stranded (ss) DNA genome of ~5.5 kb that encodes a small noncoding RNA of 140 nucleotides known as bocavirus-encoded small RNA (BocaSR), in addition to viral proteins. Here, we determined the secondary structure of BocaSR in vivo by using DMS-MaPseq. Our findings reveal that BocaSR undergoes N6-methyladenosine (m6A) modification at multiple sites, which is critical for viral DNA replication in both dividing HEK293 cells and nondividing cells of the human airway epithelium. Mechanistically, we found that m6A-modified BocaSR serves as a mediator for recruiting Y-family DNA repair DNA polymerase (Pol) η and Pol κ likely through a direct interaction between BocaSR and the viral DNA replication origin at the right terminus of the viral genome. Thus, this report represents direct involvement of a viral small noncoding RNA in viral DNA replication through m6A modification.Human bocavirus 1 (HBoV1) is a human parvovirus that causes lower respiratory tract infections in young children. It contains a single-stranded (ss) DNA genome of ~5.5 kb that encodes a small noncoding RNA of 140 nucleotides known as bocavirus-encoded small RNA (BocaSR), in addition to viral proteins. Here, we determined the secondary structure of BocaSR in vivo by using DMS-MaPseq. Our findings reveal that BocaSR undergoes N6-methyladenosine (m6A) modification at multiple sites, which is critical for viral DNA replication in both dividing HEK293 cells and nondividing cells of the human airway epithelium. Mechanistically, we found that m6A-modified BocaSR serves as a mediator for recruiting Y-family DNA repair DNA polymerase (Pol) η and Pol κ likely through a direct interaction between BocaSR and the viral DNA replication origin at the right terminus of the viral genome. Thus, this report represents direct involvement of a viral small noncoding RNA in viral DNA replication through m6A modification.
Details
- Title: Subtitle
- N6-methyladenosine modification of a parvovirus-encoded small noncoding RNA facilitates viral DNA replication through recruiting Y-family DNA polymerases
- Creators
- Kang Ning - University of Kansas Medical CenterJunxing Zhao - University of KansasZehua Feng - University of IowaSoo Yeun Park - University of IowaShane McFarlin - University of Kansas Medical CenterFang Cheng - University of Kansas Medical CenterZiying Yan - University of IowaJingxin Wang - University of KansasJianming Qiu - University of Kansas Medical Center
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.121(25), e2320782121
- Publisher
- NATL ACAD SCIENCES
- DOI
- 10.1073/pnas.2320782121
- PMID
- 38875150
- PMCID
- PMC11194592
- ISSN
- 1091-6490
- eISSN
- 1091-6490
- Grant note
- University of Iowa (National Institutes of Health (NIH): P30DK054759 National Institute of Allergy and Infectious Diseases (NIAID): AI150877, AI156448 National Institute of General Medical Sciences (NIGMS): R35 GM147498 Cystic Fibrosis Foundation Research: YAN23G0 Confocal Microscopy Core Laboratory at The University of Kansas Medical Center: S10OD 023625
We thank the members of the Jianming Qiu Laboratory for their valuable discussions. We are indebted to Dr. Jianrong Li at the Ohio State University and Dr. Yan Xiang at University of Texas Health San Antonio for the kind of research materials and valuable discussions. We thank Dr. Yanggu Shi from Arraystar Inc. for technical support of MeRIP-qPCR. We thank Dr. Joe F. Lutkenhaus from the University of Kansas Medical Center for the support of the Biolayer Interferometry assay. We are also grateful for the support from Dr. John F. Engelhardt and the Center for Gene Therapy, the University of Iowa (National Institutes of Health (NIH) Grant P30DK054759) . This study was supported by National Institute of Allergy and Infectious Diseases (NIAID) Grants AI150877 and AI156448 (Drs. Jianming Qiu and Ziying Yan) , National Institute of General Medical Sciences (NIGMS) Grant R35 GM147498 (Dr. Jingxin Wang) , and Cystic Fibrosis Foundation Research Grant YAN23G0 (Dr. Ziying Yan) . We are grateful to the Confocal Microscopy Core Laboratory at The University of Kansas Medical Center. The Stimulated Emission Depletion (STED) confocal microscope was supported by NIH Grant S10OD 023625. The funders had no role in the study design, data collection and interpretation, or the decision to submit the work for publication.
- Language
- English
- Date published
- 06/18/2024
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984644460102771
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