6fsz | pdb_00006fsz
Structure of the nuclear RNA exosome
Structural highlights
Function[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.[1] [2] [3] [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.[4] [5] [6] [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.[7] [8] [LRP1_YEAST] Required for exosome-dependent processing of pre-rRNA and small nucleolar RNA (snRNA) precursors. Involved in processing of 35S pre-rRNA at the A0, A1 and A2 sites. Required for activity of RRP6 in 7S pre-rRNA processing. Also has a role in 3'-processing of U4 and U5 small nuclear RNAs (snRNAs). Acts as a mRNA export factor. Mediates mRNA degradation upon UV irradiation. Maintains genome integrity where it is involved in both non-homologous end joining (NHEJ) and homologous recombination pathway repair of double strand DNA breaks. During NHEJ, required for joining 3'-overhanging ends. Also involved in telomere length regulation and maintenance.[9] [10] [11] [12] [13] [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.[14] [15] [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.[16] [17] [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.[18] [19] [20] [21] [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.[22] [23] [24] [25] [MTR4_YEAST] ATP-dependent RNA helicase required for the 3'-end formation of 5.8S RNA. Cofactor for the exosome complex that unwinds secondary structure in pre-rRNA. Required for nucleocytoplasmic transport of mRNA. May serve as a chaperone which translocates or normalizes the structure of mRNAs in preparation for export. Component of the TRAMP complex which has a poly(A) RNA polymerase activity and is involved in a post-transcriptional quality control mechanism limiting inappropriate expression of genetic information. Polyadenylation is required for the degradative activity of the exosome on several of its nuclear RNA substrates.[26] [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.[27] [28] [29] [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.[30] [31] [32] [33] [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.[34] [35] [36] [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.[37] [38] Publication Abstract from PubMedThe RNA exosome complex processes and degrades a wide range of transcripts, including ribosomal RNAs. We used cryo-EM to visualize the yeast nuclear exosome holo-complex captured on a precursor large ribosomal subunit (pre-60S) during 7S-to-5.8S rRNA processing. The cofactors of the nuclear exosome are sandwiched between the ribonuclease core complex (Exo-10) and the remodeled "foot" structure of the pre-60S particle, which harbors the 5.8S rRNA precursor. The exosome-associated helicase Mtr4 recognizes the preribosomal substrate by docking to specific sites on the 25S rRNA, captures the 3' extension of the 5.8S rRNA, and channels it toward Exo-10. The structure elucidates how the exosome forms a structural and functional unit together with its massive pre-60S substrate to process rRNA during ribosome maturation. Structure of the nuclear exosome captured on a maturing preribosome.,Schuller JM, Falk S, Fromm L, Hurt E, Conti E Science. 2018 Mar 8. pii: science.aar5428. doi: 10.1126/science.aar5428. PMID:29519915[39] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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