Reactome | Deadenylation-dependent mRNA decay

Deadenylation-dependent mRNA decay

Stable Identifier

R-HSA-429914

Type

Pathway

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this pathway in the Pathway Browser

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.

Literature References

PubMed ID	Title	Journal	Year
14749774	The enzymes and control of eukaryotic mRNA turnover Parker, R, Song, H	Nat Struct Mol Biol	2004
16141059	From birth to death: the complex lives of eukaryotic mRNAs Moore, MJ	Science	2005
15475613	Messenger RNA decay in mammalian cells: the exonuclease perspective Fritz, DT, Bergman, N, Kilpatrick, WJ, Wilusz, CJ, Wilusz, J	Cell Biochem Biophys	2004
19239894	The many pathways of RNA degradation Houseley, J, Tollervey, D	Cell	2009
17245413	The highways and byways of mRNA decay Garneau, NL, Wilusz, J, Wilusz, CJ	Nat Rev Mol Cell Biol	2007
11283721	The cap-to-tail guide to mRNA turnover Wilusz, CJ, Wormington, M, Peltz, SW	Nat Rev Mol Cell Biol	2001