Endogenous cellular poly-tailed small RNAs

Endogenous cellular poly-tailed small RNAs are a diverse group of RNA molecules characterized by a 3' polyadenosine (poly(A)) tail and often a 5' triphosphate moiety. These RNAs are typically generated as byproducts of RNA metabolism or through the action of non-canonical poly(A) polymerases like TENT4A and TENT4B, which mark them for degradation or stabilization. They function as potent endogenous ligands for the cytosolic sensor RIG-I (Retinoic acid-inducible gene I), which triggers the innate immune system's antiviral response. Under normal physiological conditions, these RNAs are sequestered or rapidly degraded to prevent autoimmunity; however, their accumulation can lead to chronic inflammation or interferonopathies. While they are not traditional therapeutic targets, their role in RIG-I activation makes them significant in the study of autoimmune diseases and the development of synthetic RNA-based immunotherapies for cancer.

Other names

Polyadenylated small RNAsPoly(A) small RNAs5'-triphosphate polyadenylated RNAsEndogenous RIG-I ligands

Binding and activation of the RIG-I receptor, leading to MAVS-mediated induction of type I interferons and proinflammatory cytokines.