RIPLET

Riplet is the common name for the human ubiquitin E3 ligase encoded by the RNF135 gene. It plays a key role in innate immunity by activating the RNA sensor RIG-I through ubiquitination, thereby promoting antiviral signaling.

Function and mechanism

Riplet catalyzes the attachment of K63-linked ubiquitin chains to RIG-I, primarily on its C-terminal regulatory region. This modification facilitates RIG-I activation, leading to its oligomerization and interaction with the mitochondrial antiviral signaling protein MAVS. The RIG-I–MAVS axis then triggers downstream signaling that activates transcription factors such as IRF3 and NF-κB, resulting in the production of type I interferons and other antiviral genes. While other factors such as TRIM25 can contribute to RIG-I activation in some contexts, Riplet-mediated ubiquitination is an important contributor to robust RIG-I signaling in several model systems.

Biological significance

Riplet resides in the cytoplasm and belongs to the family of RING finger E3 ligases. Genetic or functional disruption of Riplet in experimental models often leads to diminished type I interferon responses and greater viral replication, whereas increased Riplet activity can enhance antiviral signaling. The requirement for Riplet can vary by cell type and organism, reflecting a complex regulation of RIG-I–mediated sensing across species.

Clinical and research notes

Because the RIG-I pathway is central to defense against RNA viruses, Riplet is of interest in studies of immune competence and viral pathogenesis. Abnormal Riplet activity has implications for immune regulation and may inform approaches to antiviral therapies or immune modulation. See also RIG-I, MAVS, and ubiquitination pathways.