| Structural highlights
6ft6 is a 57 chain structure with sequence from Baker's yeast and Saccharomyces cerevisiae (strain atcc 204508 / s288c). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| NonStd Res: | |
| Gene: | RRP6, UNC733, YOR001W (Baker's yeast), LRP1, RRP47, YC1D, YHR081W (Baker's yeast), MTR4, DOB1, YJL050W, J1158 (Baker's yeast) |
| Activity: | RNA helicase, with EC number 3.6.4.13 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[RLP24_YEAST] Involved in the biogenesis of the 60S ribosomal subunit. Ensures the docking of NOG1 to pre-60S particles.[1] [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.[2] [3] [4] [5] [6] [NOG1_YEAST] Involved in the biogenesis of the 60S ribosomal subunit.[7] [PESC_YEAST] Component of the NOP7 complex, which is required for maturation of the 25S and 5.8S ribosomal RNAs and formation of the 60S ribosome.[HAMAP-Rule:MF_03028][8] [9] [10] [11] [RL25_YEAST] This protein binds to a specific region on the 26S rRNA. [BUD20_YEAST] Involved in positioning the proximal bud pole signal.[12] [RL11A_YEAST] Binds to 5S ribosomal RNA. [CGR1_YEAST] Involved in nucleolar integrity and required for processing of the pre-rRNA for the 60S ribosome subunit.[13] [14] [15] [IF6_YEAST] Binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit to form the 80S initiation complex in the cytoplasm. Is also involved in ribosome biogenesis. Associates with pre-60S subunits in the nucleus and is involved in its nuclear export. Cytoplasmic release of TIF6 from 60S subunits and nuclear relocalization is promoted by the GTPase RIA1/EFL1 and by SDO1. Also required for pre-rRNA processing.[16] [17] [18] [19] [20] [21] [NSA2_YEAST] Involved in the biogenesis of the 60S ribosomal subunit. May play a part in the quality control of pre-60S particles. Under normal, rapid growth conditions, high levels of NSA2 would allow the progression of pre-60S particles through the ITS2 processing.[22] [23] [RRS1_YEAST] Required for ribosome biogenesis.[24] [MRT4_YEAST] Involved in mRNA turnover and ribosome assembly. [NOG2_YEAST] GTPase that associates with pre-60S ribosomal subunits in the nucleolus and is required for their nuclear export and maturation.[25] [RL37A_YEAST] Binds to the 23S rRNA (By similarity). [NLE1_YEAST] Involved in processing and efficient intra-nuclear transport or pre-60S ribosomal subunits. Forms a complex with REA1 which is essential for ATP-dependent dissociation of a group of nonribosomal factors from the pre-60S particle.[26] [27] [28] [ARX1_YEAST] Probable metalloprotease involved in proper assembly of pre-ribosomal particles during the biogenesis of the 60S ribosomal subunit. Accompanies the pre-60S particles to the cytoplasm.[29] [30] [RL4A_YEAST] Participates in the regulation of the accumulation of its own mRNA.[31] [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.[32] [RPF2_YEAST] Required for biogenesis of the 60S ribosomal subunit.[33] [NUG1_YEAST] GTPase required for 60S ribosomal subunit export to the cytoplasm.[34] [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.[35] [36] [37] [38] [RL5_YEAST] Binds 5S RNA and is required for 60S subunit assembly.
Publication Abstract from PubMed
The 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
- ↑ Saveanu C, Namane A, Gleizes PE, Lebreton A, Rousselle JC, Noaillac-Depeyre J, Gas N, Jacquier A, Fromont-Racine M. Sequential protein association with nascent 60S ribosomal particles. Mol Cell Biol. 2003 Jul;23(13):4449-60. PMID:12808088
- ↑ Erdemir T, Bilican B, Cagatay T, Goding CR, Yavuzer U. Saccharomyces cerevisiae C1D is implicated in both non-homologous DNA end joining and homologous recombination. Mol Microbiol. 2002 Nov;46(4):947-57. PMID:12421302
- ↑ Peng WT, Robinson MD, Mnaimneh S, Krogan NJ, Cagney G, Morris Q, Davierwala AP, Grigull J, Yang X, Zhang W, Mitsakakis N, Ryan OW, Datta N, Jojic V, Pal C, Canadien V, Richards D, Beattie B, Wu LF, Altschuler SJ, Roweis S, Frey BJ, Emili A, Greenblatt JF, Hughes TR. A panoramic view of yeast noncoding RNA processing. Cell. 2003 Jun 27;113(7):919-33. PMID:12837249
- ↑ Mitchell P, Petfalski E, Houalla R, Podtelejnikov A, Mann M, Tollervey D. Rrp47p is an exosome-associated protein required for the 3' processing of stable RNAs. Mol Cell Biol. 2003 Oct;23(19):6982-92. PMID:12972615
- ↑ Askree SH, Yehuda T, Smolikov S, Gurevich R, Hawk J, Coker C, Krauskopf A, Kupiec M, McEachern MJ. A genome-wide screen for Saccharomyces cerevisiae deletion mutants that affect telomere length. Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8658-63. Epub 2004 May 25. PMID:15161972 doi:http://dx.doi.org/10.1073/pnas.0401263101
- ↑ 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
- ↑ Saveanu C, Namane A, Gleizes PE, Lebreton A, Rousselle JC, Noaillac-Depeyre J, Gas N, Jacquier A, Fromont-Racine M. Sequential protein association with nascent 60S ribosomal particles. Mol Cell Biol. 2003 Jul;23(13):4449-60. PMID:12808088
- ↑ Adams CC, Jakovljevic J, Roman J, Harnpicharnchai P, Woolford JL Jr. Saccharomyces cerevisiae nucleolar protein Nop7p is necessary for biogenesis of 60S ribosomal subunits. RNA. 2002 Feb;8(2):150-65. PMID:11911362
- ↑ Oeffinger M, Leung A, Lamond A, Tollervey D. Yeast Pescadillo is required for multiple activities during 60S ribosomal subunit synthesis. RNA. 2002 May;8(5):626-36. PMID:12022229
- ↑ Du YC, Stillman B. Yph1p, an ORC-interacting protein: potential links between cell proliferation control, DNA replication, and ribosome biogenesis. Cell. 2002 Jun 28;109(7):835-48. PMID:12110181
- ↑ Tang L, Sahasranaman A, Jakovljevic J, Schleifman E, Woolford JL Jr. Interactions among Ytm1, Erb1, and Nop7 required for assembly of the Nop7-subcomplex in yeast preribosomes. Mol Biol Cell. 2008 Jul;19(7):2844-56. doi: 10.1091/mbc.E07-12-1281. Epub 2008, Apr 30. PMID:18448671 doi:http://dx.doi.org/10.1091/mbc.E07-12-1281
- ↑ Ni L, Snyder M. A genomic study of the bipolar bud site selection pattern in Saccharomyces cerevisiae. Mol Biol Cell. 2001 Jul;12(7):2147-70. PMID:11452010
- ↑ Sun J, McFarland M, Boettner D, Panepinto J, Rhodes JC, Askew DS. Cgr1p, a novel nucleolar protein encoded by Saccharomyces cerevisiae orf YGL0292w. Curr Microbiol. 2001 Jan;42(1):65-9. PMID:11116400
- ↑ Moy TI, Boettner D, Rhodes JC, Silver PA, Askew DS. Identification of a role for Saccharomyces cerevisiae Cgr1p in pre-rRNA processing and 60S ribosome subunit synthesis. Microbiology. 2002 Apr;148(Pt 4):1081-90. PMID:11932453
- ↑ Wade CH, Umbarger MA, McAlear MA. The budding yeast rRNA and ribosome biosynthesis (RRB) regulon contains over 200 genes. Yeast. 2006 Mar;23(4):293-306. PMID:16544271 doi:http://dx.doi.org/10.1002/yea.1353
- ↑ Sanvito F, Piatti S, Villa A, Bossi M, Lucchini G, Marchisio PC, Biffo S. The beta4 integrin interactor p27(BBP/eIF6) is an essential nuclear matrix protein involved in 60S ribosomal subunit assembly. J Cell Biol. 1999 Mar 8;144(5):823-37. PMID:10085284
- ↑ Senger B, Lafontaine DL, Graindorge JS, Gadal O, Camasses A, Sanni A, Garnier JM, Breitenbach M, Hurt E, Fasiolo F. The nucle(ol)ar Tif6p and Efl1p are required for a late cytoplasmic step of ribosome synthesis. Mol Cell. 2001 Dec;8(6):1363-73. PMID:11779510
- ↑ Basu U, Si K, Warner JR, Maitra U. The Saccharomyces cerevisiae TIF6 gene encoding translation initiation factor 6 is required for 60S ribosomal subunit biogenesis. Mol Cell Biol. 2001 Mar;21(5):1453-62. PMID:11238882 doi:10.1128/MCB.21.5.1453-1462.2001
- ↑ Menne TF, Goyenechea B, Sanchez-Puig N, Wong CC, Tonkin LM, Ancliff PJ, Brost RL, Costanzo M, Boone C, Warren AJ. The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast. Nat Genet. 2007 Apr;39(4):486-95. Epub 2007 Mar 11. PMID:17353896 doi:ng1994
- ↑ Ray P, Basu U, Ray A, Majumdar R, Deng H, Maitra U. The Saccharomyces cerevisiae 60 S ribosome biogenesis factor Tif6p is regulated by Hrr25p-mediated phosphorylation. J Biol Chem. 2008 Apr 11;283(15):9681-91. doi: 10.1074/jbc.M710294200. Epub 2008 , Feb 5. PMID:18256024 doi:10.1074/jbc.M710294200
- ↑ Groft CM, Beckmann R, Sali A, Burley SK. Crystal structures of ribosome anti-association factor IF6. Nat Struct Biol. 2000 Dec;7(12):1156-64. PMID:11101899 doi:10.1038/82017
- ↑ Wade CH, Umbarger MA, McAlear MA. The budding yeast rRNA and ribosome biosynthesis (RRB) regulon contains over 200 genes. Yeast. 2006 Mar;23(4):293-306. PMID:16544271 doi:http://dx.doi.org/10.1002/yea.1353
- ↑ Lebreton A, Saveanu C, Decourty L, Jacquier A, Fromont-Racine M. Nsa2 is an unstable, conserved factor required for the maturation of 27 SB pre-rRNAs. J Biol Chem. 2006 Sep 15;281(37):27099-108. Epub 2006 Jul 21. PMID:16861225 doi:http://dx.doi.org/M602199200
- ↑ Tsuno A, Miyoshi K, Tsujii R, Miyakawa T, Mizuta K. RRS1, a conserved essential gene, encodes a novel regulatory protein required for ribosome biogenesis in Saccharomyces cerevisiae. Mol Cell Biol. 2000 Mar;20(6):2066-74. PMID:10688653
- ↑ Saveanu C, Bienvenu D, Namane A, Gleizes PE, Gas N, Jacquier A, Fromont-Racine M. Nog2p, a putative GTPase associated with pre-60S subunits and required for late 60S maturation steps. EMBO J. 2001 Nov 15;20(22):6475-84. PMID:11707418 doi:http://dx.doi.org/10.1093/emboj/20.22.6475
- ↑ de la Cruz J, Sanz-Martinez E, Remacha M. The essential WD-repeat protein Rsa4p is required for rRNA processing and intra-nuclear transport of 60S ribosomal subunits. Nucleic Acids Res. 2005 Oct 12;33(18):5728-39. Print 2005. PMID:16221974 doi:http://dx.doi.org/10.1093/nar/gki887
- ↑ Ulbrich C, Diepholz M, Bassler J, Kressler D, Pertschy B, Galani K, Bottcher B, Hurt E. Mechanochemical removal of ribosome biogenesis factors from nascent 60S ribosomal subunits. Cell. 2009 Sep 4;138(5):911-22. PMID:19737519 doi:http://dx.doi.org/S0092-8674(09)00792-2
- ↑ Bassler J, Kallas M, Pertschy B, Ulbrich C, Thoms M, Hurt E. The AAA-ATPase Rea1 drives removal of biogenesis factors during multiple stages of 60S ribosome assembly. Mol Cell. 2010 Jun 11;38(5):712-21. doi: 10.1016/j.molcel.2010.05.024. PMID:20542003 doi:http://dx.doi.org/10.1016/j.molcel.2010.05.024
- ↑ Nissan TA, Bassler J, Petfalski E, Tollervey D, Hurt E. 60S pre-ribosome formation viewed from assembly in the nucleolus until export to the cytoplasm. EMBO J. 2002 Oct 15;21(20):5539-47. PMID:12374754
- ↑ Hung NJ, Johnson AW. Nuclear recycling of the pre-60S ribosomal subunit-associated factor Arx1 depends on Rei1 in Saccharomyces cerevisiae. Mol Cell Biol. 2006 May;26(10):3718-27. PMID:16648468 doi:http://dx.doi.org/26/10/3718
- ↑ Presutti C, Ciafre SA, Bozzoni I. The ribosomal protein L2 in S. cerevisiae controls the level of accumulation of its own mRNA. EMBO J. 1991 Aug;10(8):2215-21. PMID:2065661
- ↑ Vanacova S, Wolf J, Martin G, Blank D, Dettwiler S, Friedlein A, Langen H, Keith G, Keller W. A new yeast poly(A) polymerase complex involved in RNA quality control. PLoS Biol. 2005 Jun;3(6):e189. Epub 2005 Apr 19. PMID:15828860 doi:http://dx.doi.org/05-PLBI-RA-0095R2
- ↑ Bogengruber E, Briza P, Doppler E, Wimmer H, Koller L, Fasiolo F, Senger B, Hegemann JH, Breitenbach M. Functional analysis in yeast of the Brix protein superfamily involved in the biogenesis of ribosomes. FEMS Yeast Res. 2003 Mar;3(1):35-43. PMID:12702244
- ↑ Bassler J, Grandi P, Gadal O, Lessmann T, Petfalski E, Tollervey D, Lechner J, Hurt E. Identification of a 60S preribosomal particle that is closely linked to nuclear export. Mol Cell. 2001 Sep;8(3):517-29. PMID:11583615
- ↑ 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
- ↑ Schuller JM, Falk S, Fromm L, Hurt E, Conti E. Structure of the nuclear exosome captured on a maturing preribosome. Science. 2018 Mar 8. pii: science.aar5428. doi: 10.1126/science.aar5428. PMID:29519915 doi:http://dx.doi.org/10.1126/science.aar5428
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