N6-methyladenosine modification of a parvovirus-encoded small noncoding RNA facilitates viral DNA replication through recruiting Y- family DNA polymerases

• 成果类型: Article
• 署名作者: Ning, Kang; Zhao, Junxing; Feng, Zehua; Park, Soo Yeun; Mcfarlin, Shane; Cheng, Fang; Yan, Ziying; Wang, Jingxin; Qiu, Jianming
• 署名单位: University of Kansas; University of Kansas Medical Center; University of Kansas; University of Chicago; University of Iowa
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10011
• DOI: 10.1073/pnas.2320782121
• 发表日期: 2024-06-18
• 关键词: human bocavirus; web server; methylation; expression; 5-methylcytosine; translation; map

摘要

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 similar to 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) eta and Pol kappa 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.