Reactome: A Curated Pathway Database

Deadenylation-dependent mRNA decay (R-HSA-429914) [Homo sapiens]


After undergoing rounds of translation, mRNA is normally destroyed by the deadenylation-dependent pathway. Though the trigger is unclear, deadenylation likely proceeds in two steps: one catalyzed by the PAN2-PAN3 complex that shortens the poly(A) tail from about 200 adenosine residues to about 80 residues and one catalyzed by the CCR4-NOT complex or by the PARN enzyme that shortens the tail to about 10-15 residues.
After deadenylation the mRNA is then hydrolyzed by either the 5' to 3' pathway or the 3' to 5' pathway. It is unknown what determinants target a mRNA to one pathway or the other.
The 5' to 3' pathway is initiated by binding of the Lsm1-7 complex to the 3' oligoadenylate tail followed by decapping by the DCP1-DCP2 complex. The 5' to 3' exoribonuclease XRN1 then hydrolyzes the remaining RNA.
The 3' to 5' pathway is initiated by the exosome complex at the 3' end of the mRNA. The exosome processively hydrolyzes the mRNA from 3' to 5', leaving only a capped oligoribonucleotide. The cap is then removed by the scavenging decapping enzyme DCPS.

Additional Information
Compartment cytosol
GO Biological Process nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (0000288)
Literature References
pubMedId Title Journal Year
16141059 From birth to death: the complex lives of eukaryotic mRNAs Science 2005
15475613 Messenger RNA decay in mammalian cells: the exonuclease perspective Cell Biochem Biophys 2004
11283721 The cap-to-tail guide to mRNA turnover Nat Rev Mol Cell Biol 2001
14749774 The enzymes and control of eukaryotic mRNA turnover Nat Struct Mol Biol 2004
17245413 The highways and byways of mRNA decay Nat Rev Mol Cell Biol 2007
19239894 The many pathways of RNA degradation Cell 2009