PathwayStep320 PathwayStep316 PathwayStep313 Deadenylation of mRNA mRNA Decay by 3' to 5' Exoribonuclease mRNA Decay by 5' to 3' Exoribonuclease Deadenylation-dependent mRNA decay 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.<br>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.<br>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.<br>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. Authored: May, B, 2009-07-22 Edited: May, B, 2009-07-22 GENE ONTOLOGYGO:0000288 Pubmed11283721 Pubmed14749774 Pubmed15475613 Pubmed16141059 Pubmed17245413 Pubmed19239894 Reactome Database ID Release 43429914 Reactome, http://www.reactome.org ReactomeREACT_20639 Reviewed: Wilusz, J, 2009-09-17