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N6-methyladenosine modification of a parvovirus-encoded small noncoding RNA facilitates viral DNA replication through recruiting Y-family DNA polymerases
Ning, Kang Zhao, Junxing Feng, Zehua Park, Soo Yeun McFarlin, Shane Cheng, Fang Yan, Ziying Wang, Jingxin Qiu, Jianming
Ning, Kang
Zhao, Junxing
Feng, Zehua
Park, Soo Yeun
McFarlin, Shane
Cheng, Fang
Yan, Ziying
Wang, Jingxin
Qiu, Jianming
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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.
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Date
2024-06-14
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Publisher
PNAS
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Keywords
M6A modification, Viral noncoding RNA, Parvovirus, DNA replication
Citation
Ning K, Zhao J, Feng Z, Park SY, McFarlin S, Cheng F, Yan Z, Wang J, Qiu J. N6-methyladenosine modification of a parvovirus-encoded small noncoding RNA facilitates viral DNA replication through recruiting Y-family DNA polymerases. Proc Natl Acad Sci U S A. 2024 Jun 18;121(25):e2320782121. doi: 10.1073/pnas.2320782121. Epub 2024 Jun 14. PMID: 38875150; PMCID: PMC11194592