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[[Image:2nn6.jpg|left|200px]]<br /><applet load="2nn6" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2nn6, resolution 3.35&Aring;" />
'''Structure of the human RNA exosome composed of Rrp41, Rrp45, Rrp46, Rrp43, Mtr3, Rrp42, Csl4, Rrp4, and Rrp40'''<br />


==Overview==
==Structure of the human RNA exosome composed of Rrp41, Rrp45, Rrp46, Rrp43, Mtr3, Rrp42, Csl4, Rrp4, and Rrp40==
The RNA exosome is a multisubunit 3' to 5' exoribonuclease complex that, participates in degradation and processing of cellular RNA. To determine, the activities and structure of the eukaryotic exosome, we report the, reconstitution of 9-subunit exosomes from yeast and human and, reconstitution of 10- and 11-subunit exosomes from yeast. Comparative, biochemical analysis between purified subunits and reconstituted exosomes, using AU-rich, polyadenylated (poly[A]), generic, and structured RNA, substrates reveals processive phosphorolytic activities for human, Rrp41/Rrp45 and the 9-subunit human exosome, processive hydrolytic, activities for yeast Rrp44 and the yeast 10-subunit exosome, distributive, hydrolytic activities for Rrp6, and processive and distributive hydrolytic, activities for the yeast 11-subunit exosome. To elucidate the architecture, of a eukaryotic exosome, its conserved surfaces, and the structural basis, for RNA decay, we report the X-ray structure determination for the 286 kDa, nine-subunit human exosome at 3.35 A.
<StructureSection load='2nn6' size='340' side='right'caption='[[2nn6]], [[Resolution|resolution]] 3.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2nn6]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The February 2007 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Exosomes''  by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2007_2 10.2210/rcsb_pdb/mom_2007_2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NN6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NN6 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.35&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2nn6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nn6 OCA], [https://pdbe.org/2nn6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nn6 RCSB], [https://www.ebi.ac.uk/pdbsum/2nn6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nn6 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/EXOS9_HUMAN EXOS9_HUMAN] Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. EXOSC9 binds to ARE-containing RNAs.<ref>PMID:11782436</ref> <ref>PMID:16455498</ref> <ref>PMID:16912217</ref> <ref>PMID:17545563</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nn/2nn6_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2nn6 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The RNA exosome is a multisubunit 3' to 5' exoribonuclease complex that participates in degradation and processing of cellular RNA. To determine the activities and structure of the eukaryotic exosome, we report the reconstitution of 9-subunit exosomes from yeast and human and reconstitution of 10- and 11-subunit exosomes from yeast. Comparative biochemical analysis between purified subunits and reconstituted exosomes using AU-rich, polyadenylated (poly[A]), generic, and structured RNA substrates reveals processive phosphorolytic activities for human Rrp41/Rrp45 and the 9-subunit human exosome, processive hydrolytic activities for yeast Rrp44 and the yeast 10-subunit exosome, distributive hydrolytic activities for Rrp6, and processive and distributive hydrolytic activities for the yeast 11-subunit exosome. To elucidate the architecture of a eukaryotic exosome, its conserved surfaces, and the structural basis for RNA decay, we report the X-ray structure determination for the 286 kDa nine-subunit human exosome at 3.35 A.


==About this Structure==
Reconstitution, activities, and structure of the eukaryotic RNA exosome.,Liu Q, Greimann JC, Lima CD Cell. 2006 Dec 15;127(6):1223-37. PMID:17174896<ref>PMID:17174896</ref>
2NN6 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The following page contains interesting information on the relation of 2NN6 with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb86_1.html Exosomes]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NN6 OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Reconstitution, activities, and structure of the eukaryotic RNA exosome., Liu Q, Greimann JC, Lima CD, Cell. 2006 Dec 15;127(6):1223-37. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17174896 17174896]
</div>
<div class="pdbe-citations 2nn6" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Exosome 3D structures|Exosome 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Exosomes]]
[[Category: Exosomes]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Lima, C.D.]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: exoribonuclease]]
[[Category: Lima CD]]
[[Category: exosome]]
[[Category: phosphorolytic]]
[[Category: pm/scl]]
[[Category: ribonuclease]]
[[Category: rna]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:39:18 2008''

Latest revision as of 03:08, 28 December 2023

Structure of the human RNA exosome composed of Rrp41, Rrp45, Rrp46, Rrp43, Mtr3, Rrp42, Csl4, Rrp4, and Rrp40Structure of the human RNA exosome composed of Rrp41, Rrp45, Rrp46, Rrp43, Mtr3, Rrp42, Csl4, Rrp4, and Rrp40

Structural highlights

2nn6 is a 9 chain structure with sequence from Homo sapiens. The February 2007 RCSB PDB Molecule of the Month feature on Exosomes by David S. Goodsell is 10.2210/rcsb_pdb/mom_2007_2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.35Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

EXOS9_HUMAN Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. EXOSC9 binds to ARE-containing RNAs.[1] [2] [3] [4]

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

The RNA exosome is a multisubunit 3' to 5' exoribonuclease complex that participates in degradation and processing of cellular RNA. To determine the activities and structure of the eukaryotic exosome, we report the reconstitution of 9-subunit exosomes from yeast and human and reconstitution of 10- and 11-subunit exosomes from yeast. Comparative biochemical analysis between purified subunits and reconstituted exosomes using AU-rich, polyadenylated (poly[A]), generic, and structured RNA substrates reveals processive phosphorolytic activities for human Rrp41/Rrp45 and the 9-subunit human exosome, processive hydrolytic activities for yeast Rrp44 and the yeast 10-subunit exosome, distributive hydrolytic activities for Rrp6, and processive and distributive hydrolytic activities for the yeast 11-subunit exosome. To elucidate the architecture of a eukaryotic exosome, its conserved surfaces, and the structural basis for RNA decay, we report the X-ray structure determination for the 286 kDa nine-subunit human exosome at 3.35 A.

Reconstitution, activities, and structure of the eukaryotic RNA exosome.,Liu Q, Greimann JC, Lima CD Cell. 2006 Dec 15;127(6):1223-37. PMID:17174896[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Mukherjee D, Gao M, O'Connor JP, Raijmakers R, Pruijn G, Lutz CS, Wilusz J. The mammalian exosome mediates the efficient degradation of mRNAs that contain AU-rich elements. EMBO J. 2002 Jan 15;21(1-2):165-74. PMID:11782436 doi:10.1093/emboj/21.1.165
  2. West S, Gromak N, Norbury CJ, Proudfoot NJ. Adenylation and exosome-mediated degradation of cotranscriptionally cleaved pre-messenger RNA in human cells. Mol Cell. 2006 Feb 3;21(3):437-43. PMID:16455498 doi:http://dx.doi.org/10.1016/j.molcel.2005.12.008
  3. Anderson JR, Mukherjee D, Muthukumaraswamy K, Moraes KC, Wilusz CJ, Wilusz J. Sequence-specific RNA binding mediated by the RNase PH domain of components of the exosome. RNA. 2006 Oct;12(10):1810-6. Epub 2006 Aug 15. PMID:16912217 doi:10.1261/rna.144606
  4. van Dijk EL, Schilders G, Pruijn GJ. Human cell growth requires a functional cytoplasmic exosome, which is involved in various mRNA decay pathways. RNA. 2007 Jul;13(7):1027-35. Epub 2007 Jun 1. PMID:17545563 doi:10.1261/rna.575107
  5. Liu Q, Greimann JC, Lima CD. Reconstitution, activities, and structure of the eukaryotic RNA exosome. Cell. 2006 Dec 15;127(6):1223-37. PMID:17174896 doi:10.1016/j.cell.2006.10.037

2nn6, resolution 3.35Å

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