In eukaryotic somatic cells, the poly(A) tails of most mRNAs in the cytoplasm gradually get shorter, and mRNAs with shorter poly(A) tail are translated less and degraded sooner. However, it can take many hours before an mRNA is degraded. This deadenylation and degradation process can be accelerated by microRNAs complementary to the 3′ untranslated region of an mRNA. In immature egg cells, mRNAs with shortened poly(A) tails are not degraded, but are instead stored and translationally inactive. These short tailed mRNAs are activated by cytoplasmic polyadenylation after fertilisation, during egg activation.
In animals, poly(A) ribonuclease (PARN) can bind to the 5′ cap and remove nucleotides from the poly(A) tail. The level of access to the 5′ cap and poly(A) tail is important in controlling how soon the mRNA is degraded. PARN deadenylates less if the RNA is bound by the initiation factors 4E (at the 5′ cap) and 4G (at the poly(A) tail), which is why translation reduces deadenylation. The rate of deadenylation may also be regulated by RNA-binding proteins. Additionally, RNA triple helix structures and RNA motifs such as the poly(A) tail 3’ end binding pocket retard deadenylation process and inhibit poly(A) tail removal. Once the poly(A) tail is removed, the decapping complex removes the 5′ cap, leading to a degradation of the RNA. Several other proteins are involved in deadenylation in budding yeast and human cells, most notably the CCR4-Not complex.