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 3'-exoribonuclease involved in the decay of eukaryotic mRNAs. Interestingly, PARN interacts not only with the 3' end of the mRNA but also with its 5' end as PARN contains an RRM domain that specifically binds both the poly(A) tail and the 7-methylguanosine (m(7)G) cap. The interaction of PARN with the 5' cap of mRNAs stimulates the deadenylation activity and enhances the processivity of this reaction. We have determined the crystal structure of the PARN-RRM domain with a bound m(7)G triphosphate nucleotide, revealing a novel binding mode for the m(7)G cap. The structure of the m(7)G binding pocket is located outside of the canonical RNA-binding surface of the RRM domain and differs significantly from that of other m(7)G-cap-binding proteins. The crystal structure also shows a remarkable conformational flexibility of the RRM domain, leading to a perfect exchange of two alpha-helices with an adjacent protein molecule in the crystal lattice.
Crystal structure of the RRM domain of poly(A)-specific ribonuclease reveals a novel m(7)G-cap-binding mode.,Monecke T, Schell S, Dickmanns A, Ficner R J Mol Biol. 2008 Oct 17;382(4):827-34. Epub 2008 Jul 31. PMID:18694759[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
- ↑ Monecke T, Schell S, Dickmanns A, Ficner R. Crystal structure of the RRM domain of poly(A)-specific ribonuclease reveals a novel m(7)G-cap-binding mode. J Mol Biol. 2008 Oct 17;382(4):827-34. Epub 2008 Jul 31. PMID:18694759 doi:10.1016/j.jmb.2008.07.073
