Preserving the Poly(A) Tail: Strategies Viruses Use to ‘CYA’ (Cover Your A’s)

The poly(A) tail on viral mRNAs plays an important role in gene expression, given the role of the 3' mRNA tail in mRNA stability and translation. Viruses have developed several strategies to maintain the integrity of their poly(A) tails. These include attracting stabilizing proteins through elements in the 3' untranslated regions of their mRNA, remodeling their poly(A) tails using terminal nucleotidyl transferases, and blocking deadenylase access to the terminal 3' end of their poly(A) tails using protein-protein interactions or through triple helical RNA structures. Collectively, the presence of these multiple strategies illustrates the vital overall need for viruses to maintain and preserve their poly(A) tails, highlighting a potential avenue for broad-spectrum antiviral development. In addition, poly(A) tail preservation strategies used by viruses may also be applied to RNA vaccines and therapeutics.