5c0x

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Structure of a 12-subunit nuclear exosome complex bound to structured RNAStructure of a 12-subunit nuclear exosome complex bound to structured RNA

Structural highlights

5c0x is a 12 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:RRP45, YDR280W, D9954.1 (Baker's yeast), DIS3, RRP44, YOL021C, O2197 (Baker's yeast), RRP6, UNC733, YOR001W (Baker's yeast), SKI6, ECM20, RRP41, YGR195W, G7587 (Baker's yeast), RRP43, YCR035C, YCR35C, YCR522 (Baker's yeast), RRP46, YGR095C (Baker's yeast), RRP42, YDL111C (Baker's yeast), MTR3, YGR158C, G6676 (Baker's yeast), RRP40, YOL142W (Baker's yeast), RRP4, YHR069C (Baker's yeast), CSL4, SKI4, YNL232W, N1154 (Baker's yeast)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MTR3_YEAST] 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 cryptic unstable transcripts (CUTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and in RNA surveillance pathways, preventing translation of aberrant mRNAs. 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. MTR3 is part of the hexameric ring of RNase PH domain-containing subunits proposed to form a central channel which threads RNA substrates for degradation.[1] [2] [3] [RRP6_YEAST] Nuclear-specific 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 cryptic unstable transcripts (CUTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. 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. RRP6 has 3'-5' exonuclease activity which is not modulated upon association with Exo-9 suggesting that the complex inner RNA-binding path is not used to access its active site.[4] [5] [6] [7] [RRP43_YEAST] 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 cryptic unstable transcripts (CUTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and in RNA surveillance pathways, preventing translation of aberrant mRNAs. 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. RRP43 is part of the hexameric ring of RNase PH domain-containing subunits proposed to form a central channel which threads RNA substrates for degradation.[8] [9] [10] [11] [RRP40_YEAST] 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 cryptic unstable transcripts (CUTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and in RNA surveillance pathways, preventing translation of aberrant mRNAs. 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. RRP40 as peripheral part of the Exo-9 complex is thought to stabilize the hexameric ring of RNase PH-domain subunits.[12] [13] [14] [CSL4_YEAST] 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 cryptic unstable transcripts (CUTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and in RNA surveillance pathways, preventing translation of aberrant mRNAs. 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.[15] [16] [17] [RRP41_YEAST] 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 cryptic unstable transcripts (CUTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and in RNA surveillance pathways, preventing translation of aberrant mRNAs. 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. SKI6 is part of the hexameric ring of RNase PH domain-containing subunits proposed to form a central channel which threads RNA substrates for degradation.[18] [19] [RRP4_YEAST] 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 cryptic unstable transcripts (CUTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and in RNA surveillance pathways, preventing translation of aberrant mRNAs. 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. RRP4 as peripheral part of the Exo-9 complex is thought to stabilize the hexameric ring of RNase PH-domain subunits.[20] [21] [22] [23] [RRP45_YEAST] 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 cryptic unstable transcripts (CUTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and in RNA surveillance pathways, preventing translation of aberrant mRNAs. 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. RRP45 is part of the hexameric ring of RNase PH domain-containing subunits proposed to form a central channel which threads RNA substrates for degradation.[24] [25] [RRP46_YEAST] 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 cryptic unstable transcripts (CUTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and in RNA surveillance pathways, preventing translation of aberrant mRNAs. 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. RRP46 is part of the hexameric ring of RNase PH domain-containing subunits proposed to form a central channel which threads RNA substrates for degradation.[26] [27] [RRP44_YEAST] 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 cryptic unstable transcripts (CUTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and in RNA surveillance pathways, preventing translation of aberrant mRNAs. 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. DIS3 has both 3'-5' exonuclease and endonuclease activities. The exonuclease activity of DIS3 is down-regulated upon association with Exo-9 possibly involving a conformational change in the catalytic domain and threading of the RNA substrate through the complex central channel. Structured substrates can be degraded if they have a 3' single-stranded extension sufficiently long (such as 35 nt poly(A)) to span the proposed complex inner RNA-binding path and to reach the exonuclease site provided by DIS3. Plays a role in mitotic control.[28] [29] [30] [RRP42_YEAST] 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 cryptic unstable transcripts (CUTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and in RNA surveillance pathways, preventing translation of aberrant mRNAs. 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. RRP42 is part of the hexameric ring of RNase PH domain-containing subunits proposed to form a central channel which threads RNA substrates for degradation.[31] [32]

Publication Abstract from PubMed

The eukaryotic exosome is a conserved RNA-degrading complex that functions in RNA surveillance, turnover and processing. How the same machinery can either completely degrade or precisely trim RNA substrates has long remained unexplained. Here we report the crystal structures of a yeast nuclear exosome containing the 9-subunit core, the 3'-5' RNases Rrp44 and Rrp6, and the obligate Rrp6-binding partner Rrp47 in complex with different RNAs. The combined structural and biochemical data of this 12-subunit complex reveal how a single-stranded RNA can reach the Rrp44 or Rrp6 active sites directly or can bind Rrp6 and be threaded via the central channel towards the distal RNase Rrp44. When a bulky RNA is stalled at the entrance of the channel, Rrp6-Rrp47 swings open. The results suggest how the same molecular machine can coordinate processive degradation and partial trimming in an RNA-dependent manner by a concerted swinging mechanism of the two RNase subunits.

RNA degradation paths in a 12-subunit nuclear exosome complex.,Makino DL, Schuch B, Stegmann E, Baumgartner M, Basquin C, Conti E Nature. 2015 Jul 29. doi: 10.1038/nature14865. PMID:26222026[33]

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

See Also

References

  1. ↑ Kadowaki T, Schneiter R, Hitomi M, Tartakoff AM. Mutations in nucleolar proteins lead to nucleolar accumulation of polyA+ RNA in Saccharomyces cerevisiae. Mol Biol Cell. 1995 Sep;6(9):1103-10. PMID:8534909
  2. ↑ Allmang C, Petfalski E, Podtelejnikov A, Mann M, Tollervey D, Mitchell P. The yeast exosome and human PM-Scl are related complexes of 3' --> 5' exonucleases. Genes Dev. 1999 Aug 15;13(16):2148-58. PMID:10465791
  3. ↑ Dziembowski A, Lorentzen E, Conti E, Seraphin B. A single subunit, Dis3, is essentially responsible for yeast exosome core activity. Nat Struct Mol Biol. 2007 Jan;14(1):15-22. Epub 2006 Dec 17. PMID:17173052 doi:http://dx.doi.org/nsmb1184
  4. ↑ Briggs MW, Burkard KT, Butler JS. Rrp6p, the yeast homologue of the human PM-Scl 100-kDa autoantigen, is essential for efficient 5.8 S rRNA 3' end formation. J Biol Chem. 1998 May 22;273(21):13255-63. PMID:9582370
  5. ↑ Allmang C, Petfalski E, Podtelejnikov A, Mann M, Tollervey D, Mitchell P. The yeast exosome and human PM-Scl are related complexes of 3' --> 5' exonucleases. Genes Dev. 1999 Aug 15;13(16):2148-58. PMID:10465791
  6. ↑ Burkard KT, Butler JS. A nuclear 3'-5' exonuclease involved in mRNA degradation interacts with Poly(A) polymerase and the hnRNA protein Npl3p. Mol Cell Biol. 2000 Jan;20(2):604-16. PMID:10611239
  7. ↑ Hieronymus H, Yu MC, Silver PA. Genome-wide mRNA surveillance is coupled to mRNA export. Genes Dev. 2004 Nov 1;18(21):2652-62. Epub 2004 Oct 15. PMID:15489286 doi:http://dx.doi.org/gad.1241204
  8. ↑ Mitchell P, Petfalski E, Shevchenko A, Mann M, Tollervey D. The exosome: a conserved eukaryotic RNA processing complex containing multiple 3'-->5' exoribonucleases. Cell. 1997 Nov 14;91(4):457-66. PMID:9390555
  9. ↑ Zanchin NI, Goldfarb DS. The exosome subunit Rrp43p is required for the efficient maturation of 5.8S, 18S and 25S rRNA. Nucleic Acids Res. 1999 Mar 1;27(5):1283-8. PMID:9973615
  10. ↑ Oliveira CC, Gonzales FA, Zanchin NI. Temperature-sensitive mutants of the exosome subunit Rrp43p show a deficiency in mRNA degradation and no longer interact with the exosome. Nucleic Acids Res. 2002 Oct 1;30(19):4186-98. PMID:12364597
  11. ↑ Dziembowski A, Lorentzen E, Conti E, Seraphin B. A single subunit, Dis3, is essentially responsible for yeast exosome core activity. Nat Struct Mol Biol. 2007 Jan;14(1):15-22. Epub 2006 Dec 17. PMID:17173052 doi:http://dx.doi.org/nsmb1184
  12. ↑ Allmang C, Petfalski E, Podtelejnikov A, Mann M, Tollervey D, Mitchell P. The yeast exosome and human PM-Scl are related complexes of 3' --> 5' exonucleases. Genes Dev. 1999 Aug 15;13(16):2148-58. PMID:10465791
  13. ↑ Dziembowski A, Lorentzen E, Conti E, Seraphin B. A single subunit, Dis3, is essentially responsible for yeast exosome core activity. Nat Struct Mol Biol. 2007 Jan;14(1):15-22. Epub 2006 Dec 17. PMID:17173052 doi:http://dx.doi.org/nsmb1184
  14. ↑ Schaeffer D, Tsanova B, Barbas A, Reis FP, Dastidar EG, Sanchez-Rotunno M, Arraiano CM, van Hoof A. The exosome contains domains with specific endoribonuclease, exoribonuclease and cytoplasmic mRNA decay activities. Nat Struct Mol Biol. 2009 Jan;16(1):56-62. doi: 10.1038/nsmb.1528. Epub 2008 Dec , 7. PMID:19060898 doi:http://dx.doi.org/10.1038/nsmb.1528
  15. ↑ Allmang C, Petfalski E, Podtelejnikov A, Mann M, Tollervey D, Mitchell P. The yeast exosome and human PM-Scl are related complexes of 3' --> 5' exonucleases. Genes Dev. 1999 Aug 15;13(16):2148-58. PMID:10465791
  16. ↑ Dziembowski A, Lorentzen E, Conti E, Seraphin B. A single subunit, Dis3, is essentially responsible for yeast exosome core activity. Nat Struct Mol Biol. 2007 Jan;14(1):15-22. Epub 2006 Dec 17. PMID:17173052 doi:http://dx.doi.org/nsmb1184
  17. ↑ Schaeffer D, Tsanova B, Barbas A, Reis FP, Dastidar EG, Sanchez-Rotunno M, Arraiano CM, van Hoof A. The exosome contains domains with specific endoribonuclease, exoribonuclease and cytoplasmic mRNA decay activities. Nat Struct Mol Biol. 2009 Jan;16(1):56-62. doi: 10.1038/nsmb.1528. Epub 2008 Dec , 7. PMID:19060898 doi:http://dx.doi.org/10.1038/nsmb.1528
  18. ↑ Mitchell P, Petfalski E, Shevchenko A, Mann M, Tollervey D. The exosome: a conserved eukaryotic RNA processing complex containing multiple 3'-->5' exoribonucleases. Cell. 1997 Nov 14;91(4):457-66. PMID:9390555
  19. ↑ Dziembowski A, Lorentzen E, Conti E, Seraphin B. A single subunit, Dis3, is essentially responsible for yeast exosome core activity. Nat Struct Mol Biol. 2007 Jan;14(1):15-22. Epub 2006 Dec 17. PMID:17173052 doi:http://dx.doi.org/nsmb1184
  20. ↑ Mitchell P, Petfalski E, Shevchenko A, Mann M, Tollervey D. The exosome: a conserved eukaryotic RNA processing complex containing multiple 3'-->5' exoribonucleases. Cell. 1997 Nov 14;91(4):457-66. PMID:9390555
  21. ↑ Mitchell P, Petfalski E, Tollervey D. The 3' end of yeast 5.8S rRNA is generated by an exonuclease processing mechanism. Genes Dev. 1996 Feb 15;10(4):502-13. PMID:8600032
  22. ↑ Dziembowski A, Lorentzen E, Conti E, Seraphin B. A single subunit, Dis3, is essentially responsible for yeast exosome core activity. Nat Struct Mol Biol. 2007 Jan;14(1):15-22. Epub 2006 Dec 17. PMID:17173052 doi:http://dx.doi.org/nsmb1184
  23. ↑ Schaeffer D, Tsanova B, Barbas A, Reis FP, Dastidar EG, Sanchez-Rotunno M, Arraiano CM, van Hoof A. The exosome contains domains with specific endoribonuclease, exoribonuclease and cytoplasmic mRNA decay activities. Nat Struct Mol Biol. 2009 Jan;16(1):56-62. doi: 10.1038/nsmb.1528. Epub 2008 Dec , 7. PMID:19060898 doi:http://dx.doi.org/10.1038/nsmb.1528
  24. ↑ Allmang C, Petfalski E, Podtelejnikov A, Mann M, Tollervey D, Mitchell P. The yeast exosome and human PM-Scl are related complexes of 3' --> 5' exonucleases. Genes Dev. 1999 Aug 15;13(16):2148-58. PMID:10465791
  25. ↑ Dziembowski A, Lorentzen E, Conti E, Seraphin B. A single subunit, Dis3, is essentially responsible for yeast exosome core activity. Nat Struct Mol Biol. 2007 Jan;14(1):15-22. Epub 2006 Dec 17. PMID:17173052 doi:http://dx.doi.org/nsmb1184
  26. ↑ Allmang C, Petfalski E, Podtelejnikov A, Mann M, Tollervey D, Mitchell P. The yeast exosome and human PM-Scl are related complexes of 3' --> 5' exonucleases. Genes Dev. 1999 Aug 15;13(16):2148-58. PMID:10465791
  27. ↑ Dziembowski A, Lorentzen E, Conti E, Seraphin B. A single subunit, Dis3, is essentially responsible for yeast exosome core activity. Nat Struct Mol Biol. 2007 Jan;14(1):15-22. Epub 2006 Dec 17. PMID:17173052 doi:http://dx.doi.org/nsmb1184
  28. ↑ Noguchi E, Hayashi N, Azuma Y, Seki T, Nakamura M, Nakashima N, Yanagida M, He X, Mueller U, Sazer S, Nishimoto T. Dis3, implicated in mitotic control, binds directly to Ran and enhances the GEF activity of RCC1. EMBO J. 1996 Oct 15;15(20):5595-605. PMID:8896453
  29. ↑ Mitchell P, Petfalski E, Shevchenko A, Mann M, Tollervey D. The exosome: a conserved eukaryotic RNA processing complex containing multiple 3'-->5' exoribonucleases. Cell. 1997 Nov 14;91(4):457-66. PMID:9390555
  30. ↑ Dziembowski A, Lorentzen E, Conti E, Seraphin B. A single subunit, Dis3, is essentially responsible for yeast exosome core activity. Nat Struct Mol Biol. 2007 Jan;14(1):15-22. Epub 2006 Dec 17. PMID:17173052 doi:http://dx.doi.org/nsmb1184
  31. ↑ Mitchell P, Petfalski E, Shevchenko A, Mann M, Tollervey D. The exosome: a conserved eukaryotic RNA processing complex containing multiple 3'-->5' exoribonucleases. Cell. 1997 Nov 14;91(4):457-66. PMID:9390555
  32. ↑ Dziembowski A, Lorentzen E, Conti E, Seraphin B. A single subunit, Dis3, is essentially responsible for yeast exosome core activity. Nat Struct Mol Biol. 2007 Jan;14(1):15-22. Epub 2006 Dec 17. PMID:17173052 doi:http://dx.doi.org/nsmb1184
  33. ↑ Makino DL, Schuch B, Stegmann E, Baumgartner M, Basquin C, Conti E. RNA degradation paths in a 12-subunit nuclear exosome complex. Nature. 2015 Jul 29. doi: 10.1038/nature14865. PMID:26222026 doi:http://dx.doi.org/10.1038/nature14865

5c0x, resolution 3.81Å

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