Adenovirus virus-associated RNA (VA RNA)

Adenovirus virus-associated RNA (VA RNA) is a small, non-coding RNA molecule (approximately 160 nucleotides) transcribed by RNA polymerase III during the late phase of adenovirus infection (Mathews & Shenk, 1991). It exists in two distinct species, VA RNAI and VA RNAII, with VA RNAI being the primary effector in subverting host cell defenses (Vachon & Conn, 2016). The most well-characterized function of VA RNAI is its ability to bind and inhibit the double-stranded RNA-activated protein kinase (PKR), thereby preventing the phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2α) and ensuring the continued translation of viral mRNAs (Mathews & Shenk, 1991). Beyond PKR inhibition, VA RNA acts as a competitive substrate for the cellular RNA interference (RNAi) machinery, specifically saturating Exportin-5 and the Dicer enzyme, which suppresses the processing of host microRNAs (Lu & Cullen, 2004). In therapeutic contexts, VA RNA is a target for the development of novel antiviral agents, such as antisense oligonucleotides, and its deletion is a common strategy in the engineering of attenuated or oncolytic adenoviruses to enhance tumor selectivity and safety (Vachon & Conn, 2016).

Other names

VAI RNAVAII RNAVirus-associated RNAAdenovirus VA RNAIAdenovirus VA RNAII

Direct binding and inhibition of Protein Kinase R (PKR) to prevent eIF2α phosphorylation; saturation of Exportin-5 and Dicer to inhibit host RNAi pathways.