A viral noncoding RNA is a master regulator of gene expression that defines host cell identity and function

Viruses extensively reprogram the host cell to promote infection and persistence, yet the contribution of noncoding RNAs (ncRNAs) to this viral reengineering remains largely unknown. Here, we show that HSUR1, a viral Sm-class ncRNA abundantly expressed by the oncogenic Herpesvirus saimiri, functions as a master regulator of host gene expression. HSUR1 interacts with hundreds of cellular messenger RNAs (mRNAs) that encode factors involved in RNA metabolism, immune cell differentiation, and apoptosis, thereby rewiring the host transcriptome to control both cell survival and fate. Mechanistically, we show that HSUR1 acts as an RNA adaptor that coordinates the recruitment of the host microRNA miR-142-3p and AU-rich element-binding proteins to target mRNA 3' untranslated regions, redirecting post-transcriptional regulation. These findings reveal that a single viral ncRNA can orchestrate global remodeling of host gene expression, uncovering an RNA-based strategy for viral control of cell identity and function.