Model of how sequestration of hTREX by ORF57 leads to R-loops and genome instability.

<p>In a healthy cell, components of hTREX are recruited to cellular pre-mRNA during the inter-linked processes of transcription and splicing. These components then act to stabilise the newly transcribed mRNA. In situations when hTREX is rendered non-functional through mutation or siRNA, the newly transcribed mRNA can become unstable and anneal to the template strand of DNA forming R-loops and leading to an increase in DNA strand breaks. During KSHV infection or exogenous ORF57 expression, ORF57 recruits the hTREX complex, essentially replicating a system of mutated hTREX and leading to an increase in genome instability.