mRNA degradation

After export to the cytoplasm, mRNA is protected from degradation by a 5’ cap structure and a 3’ poly adenine tail. In the deadenylation dependent mRNA decay pathway, the polyA tail is gradually shortened by exonucleases. This ultimately attracts the degradation machinery that rapidly degrades the mRNA in both in the 5’ to 3’ direction and in the 3’ to 5’ direction. Additional mechanisms, including the nonsense mediated decay pathway, bypass the need for deadenylation and can remove the mRNA from the transcriptional pool independently



Inside eukaryotic cells, there is a balance between the processes of translation and mRNA decay. Messages that are being actively translated are bound by ribosomes, the eukaryotic initiation factors eIF-4E and eIF-4G, and poly(A)-binding protein. eIF-4E and eIF-4G block the decapping enzyme (DCP2), and poly(A)-binding protein blocks the exosome complex, protecting the ends of the message. The balance between translation and decay is reflected in the size and abundance of cytoplasmic structures known as P-bodies

The presence of AU-rich elements in some mammalian mRNAs tends to destabilize those transcripts through the action of cellular proteins that bind these sequences and stimulate poly(A) tail removal.

Binding of a miRNA to a message can repress translation of that message and accelerate poly(A) tail removal, thereby hastening mRNA degradation.

Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that exists in all eukaryotes. Its main function is to reduce errors in gene expression by eliminating mRNA transcripts that contain premature stop codons.