| Structural highlights
Function
[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.[1] [2] [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.[3] [4] [5] [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.[6] [7]
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 exosome is a conserved macromolecular complex essential for RNA degradation. The nine-subunit core of the eukaryotic exosome shares a similar barrel-like architecture with prokaryotic complexes, but is catalytically inert. Here, we investigate how the Rrp44 nuclease functions in the active ten-subunit exosome. The 3.0 A resolution crystal structure of the yeast Rrp44-Rrp41-Rrp45 complex shows how the nuclease interacts with the exosome core and the relative accessibility of its endoribonuclease and exoribonuclease sites. Biochemical studies indicate that RNAs thread through the central channel of the core to reach the Rrp44 exoribonuclease site. This channeling mechanism involves evolutionary conserved residues. It allows the processive unwinding and degradation of RNA duplexes containing a sufficiently long single-stranded 3' extension, without the requirement for helicase activities. Although the catalytic function of the exosome core has been lost during evolution, the substrate recruitment and binding properties have been conserved from prokaryotes to eukaryotes.
The yeast exosome functions as a macromolecular cage to channel RNA substrates for degradation.,Bonneau F, Basquin J, Ebert J, Lorentzen E, Conti E Cell. 2009 Oct 30;139(3):547-59. PMID:19879841[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Bonneau F, Basquin J, Ebert J, Lorentzen E, Conti E. The yeast exosome functions as a macromolecular cage to channel RNA substrates for degradation. Cell. 2009 Oct 30;139(3):547-59. PMID:19879841 doi:S0092-8674(09)01116-7
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