School of Molecular and Cellular Biology, Faculty of Biological Sciences, Astbury Centre of Structural Molecular Biology, University of Leeds, Leeds, United Kingdom; Astbury Centre of Structural Molecular Biology, University of Leeds, Leeds, United Kingdom
Agne Antanaviciute
Leeds Institute of Medical Research, School of Medicine, University of Leeds, St James's University Hospital, Leeds, United Kingdom
Ivaylo D Yonchev
Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, United Kingdom; Sheffield Institute For Nucleic Acids, University of Sheffield, Sheffield, United Kingdom
Ian M Carr
Leeds Institute of Medical Research, School of Medicine, University of Leeds, St James's University Hospital, Leeds, United Kingdom
Stuart A Wilson
Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, United Kingdom; Sheffield Institute For Nucleic Acids, University of Sheffield, Sheffield, United Kingdom
School of Molecular and Cellular Biology, Faculty of Biological Sciences, Astbury Centre of Structural Molecular Biology, University of Leeds, Leeds, United Kingdom; Astbury Centre of Structural Molecular Biology, University of Leeds, Leeds, United Kingdom; Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, South Africa
N6-methyladenosine (m6A) is the most abundant internal RNA modification of cellular mRNAs. m6A is recognised by YTH domain-containing proteins, which selectively bind to m6A-decorated RNAs regulating their turnover and translation. Using an m6A-modified hairpin present in the Kaposi’s sarcoma associated herpesvirus (KSHV) ORF50 RNA, we identified seven members from the ‘Royal family’ as putative m6A readers, including SND1. RIP-seq and eCLIP analysis characterised the SND1 binding profile transcriptome-wide, revealing SND1 as an m6A reader. We further demonstrate that the m6A modification of the ORF50 RNA is critical for SND1 binding, which in turn stabilises the ORF50 transcript. Importantly, SND1 depletion leads to inhibition of KSHV early gene expression showing that SND1 is essential for KSHV lytic replication. This work demonstrates that members of the ‘Royal family’ have m6A-reading ability, greatly increasing their epigenetic functions beyond protein methylation.
