Influenza A virus polymerase acidic gene RNA (PA RNA)

The Influenza A virus PA gene RNA, also known as Segment 3, is a negative-sense, single-stranded RNA molecule that constitutes one of the eight segments of the influenza A virus genome (NIH, 2025). It primarily encodes the polymerase acidic (PA) protein, a vital subunit of the viral RNA-dependent RNA polymerase (RdRp) complex, and the accessory protein PA-X through ribosomal frameshifting (Frontiers in Cellular and Infection Microbiology, 2025). The PA protein is essential for viral replication and transcription, specifically providing the cap-dependent endonuclease activity required for cap-snatching, a process where the virus steals 5' caps from host mRNAs to prime its own mRNA synthesis (NIH, 2024). Because of its critical role, the PA gene and its protein product are major targets for antiviral therapy. Baloxavir marboxil is a clinically approved drug that targets the PA protein's endonuclease domain, effectively halting viral replication (NIH, 2021). Other approved PA inhibitors include suraxavir marboxil and seloxavir marboxil, which share a similar mechanism of action (NIH, 2025). Additionally, the PA gene RNA itself is a target for experimental RNA interference (RNAi) therapies, such as siRNAs, which aim to degrade the viral transcripts and prevent protein expression (PNAS, 2004). Monitoring for mutations like I38T in the PA gene is crucial for managing clinical resistance and ensuring treatment efficacy (ResearchGate, 2025).

Other names

Segment 3 RNAPA vRNAPA mRNAPolymerase acidic gene RNAInfluenza A virus segment 3

Baloxavir marboxil and its derivatives (suraxavir, seloxavir, pixavir) act as cap-dependent endonuclease inhibitors by binding to the N-terminal domain of the PA protein, thereby blocking the cap-snatching process necessary for viral mRNA synthesis (NIH, 2024). Favipiravir acts as a nucleoside analogue that is incorporated into the viral RNA, leading to chain termination or lethal mutagenesis (NIH, 2025). Experimental siRNAs target the PA gene RNA for sequence-specific degradation via the RNA-induced silencing complex (RISC) (PNAS, 2004).