The Tudor SND1 protein is an m(6)A RNA reader essential for replication of Kaposi’s sarcoma-associated herpesvirus

Baquero-Perez, Belinda; Antanaviciute, Agne; Yonchev, Ivaylo D; Carr, Ian M; Wilson, Stuart A; Whitehouse, Adrian

N(6)-methyladenosine (m(6)A) is the most abundant internal RNA modification of cellular mRNAs. m(6)A is recognised by YTH domain-containing proteins, which selectively bind to m(6)A-decorated RNAs regulating their turnover and translation. Using an m(6)A-modified hairpin present in the Kaposi’s sarcoma associated herpesvirus (KSHV) ORF50 RNA, we identified seven members from the ‘Royal family’ as putative m(6)A readers, including SND1. RIP-seq and eCLIP analysis characterised the SND1 binding profile transcriptome-wide, revealing SND1 as an m(6)A reader. We further demonstrate that the m(6)A 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 m(6)A-reading ability, greatly increasing their epigenetic functions beyond protein methylation.