| Structural highlights
Function
PARN_HUMAN 3'-exoribonuclease that has a preference for poly(A) tails of mRNAs, thereby efficiently degrading poly(A) tails. Exonucleolytic degradation of the poly(A) tail is often the first step in the decay of eukaryotic mRNAs and is also used to silence certain maternal mRNAs translationally during oocyte maturation and early embryonic development. Interacts with both the 3'-end poly(A) tail and the 5'-end cap structure during degradation, the interaction with the cap structure being required for an efficient degradation of poly(A) tails. Involved in nonsense-mediated mRNA decay, a critical process of selective degradation of mRNAs that contain premature stop codons. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly via its interaction with KHSRP. Probably mediates the removal of poly(A) tails of AREs mRNAs, which constitutes the first step of destabilization.[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Poly(A)-specific ribonuclease (PARN) is a processive, poly(A)-specific 3' exoribonuclease. The crystal structure of C-terminal truncated human PARN determined in two states (free and RNA-bound forms) reveals that PARNn is folded into two domains, an R3H domain and a nuclease domain similar to those of Pop2p and epsilon186. The high similarity of the active site structures of PARNn and epsilon186 suggests that they may have a similar catalytic mechanism. PARNn forms a tight homodimer, with the R3H domain of one subunit partially enclosing the active site of the other subunit and poly(A) bound in a deep cavity of its nuclease domain in a sequence-nonspecific manner. The R3H domain and, possibly, the cap-binding domain are involved in poly(A) binding but these domains alone do not appear to contribute to poly(A) specificity. Mutations disrupting dimerization abolish both the enzymatic and RNA-binding activities, suggesting that the PARN dimer is a structural and functional unit. The cap-binding domain may act in concert with the R3H domain to amplify the processivity of PARN.
Structural insight into poly(A) binding and catalytic mechanism of human PARN.,Wu M, Reuter M, Lilie H, Liu Y, Wahle E, Song H EMBO J. 2005 Dec 7;24(23):4082-93. Epub 2005 Nov 10. PMID:16281054[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Korner CG, Wormington M, Muckenthaler M, Schneider S, Dehlin E, Wahle E. The deadenylating nuclease (DAN) is involved in poly(A) tail removal during the meiotic maturation of Xenopus oocytes. EMBO J. 1998 Sep 15;17(18):5427-37. PMID:9736620 doi:http://dx.doi.org/10.1093/emboj/17.18.5427
- ↑ Gao M, Fritz DT, Ford LP, Wilusz J. Interaction between a poly(A)-specific ribonuclease and the 5' cap influences mRNA deadenylation rates in vitro. Mol Cell. 2000 Mar;5(3):479-88. PMID:10882133
- ↑ Martinez J, Ren YG, Nilsson P, Ehrenberg M, Virtanen A. The mRNA cap structure stimulates rate of poly(A) removal and amplifies processivity of degradation. J Biol Chem. 2001 Jul 27;276(30):27923-9. Epub 2001 May 18. PMID:11359775 doi:http://dx.doi.org/10.1074/jbc.M102270200
- ↑ Lai WS, Kennington EA, Blackshear PJ. Tristetraprolin and its family members can promote the cell-free deadenylation of AU-rich element-containing mRNAs by poly(A) ribonuclease. Mol Cell Biol. 2003 Jun;23(11):3798-812. PMID:12748283
- ↑ Gherzi R, Lee KY, Briata P, Wegmuller D, Moroni C, Karin M, Chen CY. A KH domain RNA binding protein, KSRP, promotes ARE-directed mRNA turnover by recruiting the degradation machinery. Mol Cell. 2004 Jun 4;14(5):571-83. PMID:15175153 doi:http://dx.doi.org/10.1016/j.molcel.2004.05.002
- ↑ Wu M, Reuter M, Lilie H, Liu Y, Wahle E, Song H. Structural insight into poly(A) binding and catalytic mechanism of human PARN. EMBO J. 2005 Dec 7;24(23):4082-93. Epub 2005 Nov 10. PMID:16281054
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