Monica C. Pillon, PhD, is senior author on a new study that provides a detailed structure of the human SLFN14 enzyme that is critical for antiviral defense and platelet function.
Enzyme’s Potential Role in Immunity and Disease Studied
By Dirk Hoffman
Published July 22, 2025
Monica C. Pillon, PhD, assistant professor of structural biology in the Jacobs School of Medicine and Biomedical Sciences, is senior author on a new study that provides a detailed structure of a human enzyme critical for antiviral defense and platelet function.
“CryoEM Structure of the SLFN14 Endoribonuclease Reveals Insight Into RNA Binding and Cleavage,” was published online July 1 in the journal Nature Communications.
The study began while Pillon was an assistant professor at Baylor College of Medicine in Texas and continues in her UB lab. Pillon joined the Jacobs School in 2024.
Shedding Light on How the Enzyme Targets RNA
Through biochemistry and advanced imaging, the research uncovered the molecular principles underlying SLFN14’s RNA processing activity, Pillon says.
“Gene dysregulation is a hallmark and major culprit of disease. A central determinant of gene expression is RNA abundance, which is fundamentally the balance of RNA synthesis and RNA decay,” she says.
“While groundbreaking research has focused on dysregulated mRNA synthesis, comparatively little is known about how RNA processing and decay pathways contribute to gene regulation and disease.”
“Ribonucleases are the centerpiece to many RNA processing and decay pathways,” Pillon adds. “For this reason, my research program focuses on understudied ribonucleases, like SLFN14, to understand their vital role in defining eukaryotic gene expression and cell fate.”
During a viral infection, SLFN14 is activated to repress gene expression and limit viral replication. However, exactly how this happens is still an active area of research.
“For platelet function, SLFN14 is important for megakaryocyte differentiation and maturation,” Pillon says. “Patients with mutations to the SLFN14 gene can have decreased megakaryocyte maturation and proplatelet formation.”
Seeking Path for Restoring Platelet Production
SLFN14 dysregulation is linked to human diseases, including ribosomopathies and inherited thrombocytopenia, a bleeding disorder that is often characteristic of low platelet count and low platelet activation.
Patients with SLFN14-related inherited thrombocytopenia often show excessive bleeding, according to Pillon.
The researchers used powerful electron microscopes to take detailed pictures of the human SLFN14 enzyme to understand how it captures specific RNA molecules to control gene expression.
“These findings shed light on how the SLFN14 enzyme may target RNA to repress protein translation,” Pillon says.
“This work contributes to our growing understanding of how SLFN14 regulates gene expression to restrict viral replication,” she adds. “For patients with SLFN14-related inherited thrombocytopenia, these insights could pave the way for a potential therapeutic strategy to restore proper platelet production.”
Hannah Schneiderman, a research technician in the Department of Structural Biology in the Jacobs School, is a co-author on the paper.
Co-first authors, Justin Van Riper and Arleth O. Martinez-Claros, along with other co-authors, are from Baylor College of Medicine.