Epigenetic regulation of DPP4 receptor expression by NONO enables replication of MERS-CoV

Middle East respiratory syndrome coronavirus (MERS-CoV), initially identified in 2012, belongs to the Betacoronavirus family, alongside SARS-CoV and SARS-CoV-2. MERS-CoV transmission among humans is limited but has caused repeated spillover incidents in at least 27 countries, prompting worries about future outbreaks. Coronaviruses (CoVs) heavily depend on host proteins for their replication.

Several studies have linked the paraspeckle non-POU domain-containing octamer-binding protein (NONO) to RNA-binding proteins (RBPs) that bind to CoV genomes, although the protein's specific role in regulating replication is unclear. In this study, researchers demonstrate that NONO is essential for the expression of dipeptidyl peptidase 4 (DPP4, also known as CD26), the primary cellular receptor responsible for MERS-CoV attachment and entry.

NONO does not influence DPP4 mRNA processing or stability; instead, it promotes DPP4 transcription by controlling active H3K4me3 and repressive H3K27me3 histone modifications at the DPP4 site. The findings identify NONO as a crucial proviral host factor for MERS-CoV and uncover an epigenetic mechanism connecting a host RBP to the expression of the viral entry receptor, potentially serving as a target for therapeutic interventions.