oligoadenylates

Oligoadenylates refer to short polymers of adenosine residues linked by 2',5'-phosphodiester bonds. In the context of cellular innate immunity, the term typically denotes 2-5A oligoadenylates produced in response to double-stranded RNA during viral infection. These molecules are synthesized from ATP by the enzyme family known as 2',5'-oligoadenylate synthetases (OAS), whose expression is induced by interferons.

The primary role of 2-5A oligoadenylates is to activate RNase L, an endoribonuclease that is normally latent in cells. Binding of 2-5A to RNase L promotes its dimerization and activation, leading to degradation of single-stranded RNA. This RNA destruction reduces viral replication and can also impact host RNA, contributing to an antiviral state. The downstream effects may include inhibition of protein synthesis and, in some contexts, the induction of apoptosis.

Length and composition of 2-5A molecules can vary, with short oligoadenylates consisting of a few adenosines observed in cells, and longer species studied in research. The 2-5A signaling is tightly regulated, and its signal is terminated by cellular phosphodiesterases that hydrolyze the 2',5'-linkages, such as 2',5'-oligoadenylate phosphodiesterases, ensuring that RNase L activity is reversible.

Beyond basic biology, the OAS/RNase L pathway is explored in antiviral research and is relevant to discussions of immune responses to viral infections and related pathologies.