Structural highlights
Function
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.[1] [2] [3] [4]
Publication Abstract from PubMed
The exosome is a conserved multi-subunit ribonuclease complex that functions in 3' end processing, turnover and surveillance of nuclear and cytoplasmic RNAs. In the yeast nucleus, the 10-subunit core complex of the exosome (Exo-10) physically and functionally interacts with the Rrp6 exoribonuclease and its associated cofactor Rrp47, the helicase Mtr4 and Mpp6. Here, we show that binding of Mtr4 to Exo-10 in vitro is dependent upon both Rrp6 and Rrp47, whereas Mpp6 binds directly and independently of other cofactors. Crystallographic analyses reveal that the N-terminal domains of Rrp6 and Rrp47 form a highly intertwined structural unit. Rrp6 and Rrp47 synergize to create a composite and conserved surface groove that binds the N-terminus of Mtr4. Mutation of conserved residues within Rrp6 and Mtr4 at the structural interface disrupts their interaction and inhibits growth of strains expressing a C-terminal GFP fusion of Mtr4. These studies provide detailed structural insight into the interaction between the Rrp6-Rrp47 complex and Mtr4, revealing an important link between Mtr4 and the core exosome.
The exosome-binding factors Rrp6 and Rrp47 form a composite surface for recruiting the Mtr4 helicase.,Schuch B, Feigenbutz M, Makino DL, Falk S, Basquin C, Mitchell P, Conti E EMBO J. 2014 Oct 15. pii: e201488757. PMID:25319414[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Schuch B, Feigenbutz M, Makino DL, Falk S, Basquin C, Mitchell P, Conti E. The exosome-binding factors Rrp6 and Rrp47 form a composite surface for recruiting the Mtr4 helicase. EMBO J. 2014 Oct 15. pii: e201488757. PMID:25319414 doi:http://dx.doi.org/10.15252/embj.201488757
