4xr7 | pdb_00004xr7
Structure of the Saccharomyces cerevisiae PAN2-PAN3 core complex
Structural highlights
Function[PAN2_YEAST] Catalytic subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of two cytoplasmic mRNA deadenylases involved in mRNA turnover. PAN specifically shortens poly(A) tails of RNA when the poly(A) stretch is bound by poly(A)-binding protein PAB1, which is followed by rapid degradation of the shortened mRNA tails by the CCR4-NOT complex. Deadenylated mRNAs are then degraded by two alternative mechanisms, namely exosome-mediated 3'-5' exonucleolytic degradation, or deadenlyation-dependent mRNA decaping by DCP1-DCP2 and subsequent 5'-3' exonucleolytic degradation by XRN1. May also be involved in post-transcriptional maturation of mRNA poly(A) tails, trimming the tails from their synthesized length to the slightly shorter, apparently messenger-specific length found on newly exported mRNAs. PAN cooperates with protein kinase DUN1 in the regulation of RAD5 mRNA levels and cell survival in response to replicational stress.[1] [2] [3] [4] [5] [6] [7] [8] [PAN3_YEAST] Regulatory subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of two cytoplasmic mRNA deadenylases involved in mRNA turnover. PAN specifically shortens poly(A) tails of RNA when the poly(A) stretch is bound by poly(A)-binding protein PAB1, which is followed by rapid degradation of the shortened mRNA tails by the CCR4-NOT complex. Deadenylated mRNAs are then degraded by two alternative mechanisms, namely exosome-mediated 3'-5' exonucleolytic degradation, or deadenlyation-dependent mRNA decaping by DCP1-DCP2 and subsequent 5'-3' exonucleolytic degradation by XRN1. May also be involved in post-transcriptional maturation of mRNA poly(A) tails, trimming the tails from their synthesized length to the slightly shorter, apparently messenger-specific length found on newly exported mRNAs.. PAN3 acts as a positive regulator for PAN activity, recruiting the catalytic subunit PAN2 to mRNA via its interaction with PAB1. PAN cooperates with protein kinase DUN1 in the regulation of RAD5 mRNA levels and cell survival in response to replicational stress.[9] [10] [11] [12] [13] Publication Abstract from PubMedPan2-Pan3 is a conserved complex involved in the shortening of mRNA poly(A) tails, the initial step in eukaryotic mRNA turnover. We show that recombinant Saccharomyces cerevisiae Pan2-Pan3 can deadenylate RNAs in vitro without needing the poly(A)-binding protein Pab1. The crystal structure of an active ~200-kDa core complex reveals that Pan2 and Pan3 interact with an unusual 1:2 stoichiometry imparted by the asymmetric nature of the Pan3 homodimer. An extended region of Pan2 wraps around Pan3 and provides a major anchoring point for complex assembly. A Pan2 module formed by the pseudoubiquitin-hydrolase and RNase domains latches onto the Pan3 pseudokinase with intertwined interactions that orient the deadenylase active site toward the A-binding site of the interacting Pan3. The molecular architecture of Pan2-Pan3 suggests how the nuclease and its pseudokinase regulator act in synergy to promote deadenylation. The structure of the Pan2-Pan3 core complex reveals cross-talk between deadenylase and pseudokinase.,Schafer IB, Rode M, Bonneau F, Schussler S, Conti E Nat Struct Mol Biol. 2014 Jun 1. doi: 10.1038/nsmb.2834. PMID:24880344[14] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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