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Deadenylation-dependent decay in Homo sapiens

5'-3' exoribonuclease 1
Poly(A)-specific ribonuclease PARN
Scavenger mRNA-decapping enzyme DcpS
CCr4-NOT (CNOT7-CNOT6) complex
CCr4-NOT (CNOT7-CNOT6L) complex
CCr4-NOT (CNOT8-CNOT6) complex
CCr4-NOT (CNOT8-CNOT6L) complex
DCP1-DCP2 decapping complex
Lsm1-7 Complex
PAN2-PAN3 Complex

Deadenylation-dependent decay in REACTOME: REACT_2063

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:

  1. one catalyzed by the PAN2-PAN3 complex that shortens the poly(A) tail from about 200 adenosine residues to about 80 residues
  2. 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.

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Last modification of this entry: June 21, 2012.

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