Pathway: Deadenylation of mRNA
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Deadenylation of mRNA
Deadenylation of mRNA proceeds in two steps. According to current models, in the first step the poly(A) tail is shortened from about 200 adenosine residues to about 80 residues by the PAN2-PAN3 complex. In the second step the poly(A) tail is further shortened to 10-15 residues by either the CCR4-NOT complex or by the PARN exoribonuclease. How a particular mRNA is targeted to CCR4-NOT or PARN is unknown.
A number of other deadenylase enzymes can be identified in genomic searches. One particularly interesting one is nocturin, a protein that is related to the CCR-1 deadenylase and plays a role in circadian rhythms.
There is also evidence for networking between deadenylation and other aspects of gene expression. CCR4-NOT, for example, is known to be a transcription factor. PARN is part of a complex that regulates poly(A) tail length and hence translation in developing oocytes.
A number of other deadenylase enzymes can be identified in genomic searches. One particularly interesting one is nocturin, a protein that is related to the CCR-1 deadenylase and plays a role in circadian rhythms.
There is also evidence for networking between deadenylation and other aspects of gene expression. CCR4-NOT, for example, is known to be a transcription factor. PARN is part of a complex that regulates poly(A) tail length and hence translation in developing oocytes.
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.
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.
This superpathway encompasses the processes by which RNA transcription products are further modified covalently and non-covalently to yield their mature forms, and the regulation of these processes. Annotated pathways include ones for capping, splicing, and 3'-cleavage and polyadenylation to yield mature mRNA molecules that are exported from the nucleus (Hocine et al. 2010). mRNA editing and nonsense-mediated decay are also annotated. Processes leading to mRNA breakdown are described: deadenylation-dependent mRNA decay, microRNA-mediated RNA cleavage, and regulation of mRNA stability by proteins that bind AU-rich elements.psnRNP assembly is also annotated here.
The aminoacylation of mature tRNAs is annotated in the "Metabolism of proteins" superpathway, as a part of "Translation".