FAD Is More Than a Metabolic Cofactor: Non-Canonical RNA Cap May Be an Antiviral Target

Flavin adenine dinucleotide (FAD), a derivative of vitamin B2, has long been regarded as an important coenzyme in cellular energy metabolism. A recent review points out that FAD can also be added directly by RNA polymerases to the 5′ end of RNA during transcription initiation, forming a “non-canonical RNA cap.” Unlike the common eukaryotic m7G cap, this cap has been found in viruses, bacteria, yeast, and mammals.

The FAD cap is not merely decorative. It can affect RNA stability, degradation, and cellular functions. The most striking example is hepatitis C virus (HCV): about 75% of HCV transcripts carry an FAD cap. This cap not only participates in viral replication but also helps the virus evade RIG-I innate immune recognition, thereby suppressing interferon and inflammatory responses. This suggests that the FAD cap may be a virus-specific “disguise” and a new target for antiviral drugs.

Cells also have a set of decapping enzymes, such as DXO/Rai1, Nudt2, Nudt16, and Xrn1/Rat1, which can remove the FAD cap and initiate RNA degradation. With the development of detection techniques such as CapQuant, FAD-capQ, and CapZyme-seq, scientists can identify FAD-modified RNA more precisely.

Overall, research on FAD-RNA caps is still in its early stages, but it has revealed a new layer of RNA regulation and shown potential in antiviral and immunotherapy fields.

FOR DETAIL:  https://doi.org/10.1016/j.abb.2025.110326

Article from: