| Structural highlights
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Function
[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.[1] [2] [NOG1_YEAST] Involved in the biogenesis of the 60S ribosomal subunit.[3] [CGR1_YEAST] Involved in nucleolar integrity and required for processing of the pre-rRNA for the 60S ribosome subunit.[4] [5] [6] [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][7] [8] [9] [10] [RRS1_YEAST] Required for ribosome biogenesis.[11] [RL25_YEAST] This protein binds to a specific region on the 26S rRNA. [RL11A_YEAST] Binds to 5S ribosomal RNA. [CIC1_YEAST] An adapter protein that specifically links the 26S proteasome to its substrate CDC4 which is one of the substrate recognition subunits of the SCF E3 ubiquitin ligase complex. Required for turnover of cell cycle regulatory proteins CDC4 and GRR1. Required for synthesis and nuclear export of 60S ribosomal subunits. Required for vegetative growth.[12] [13] [RPF2_YEAST] Required for biogenesis of the 60S ribosomal subunit.[14] [RLP7_YEAST] Involved in the biogenesis of the 60S ribosomal subunit. May act as a specificity factor that binds precursor rRNAs and tethers the enzymes that carry out the early 5' to 3' exonucleolytic reactions that generate the mature rRNAs.[15] [MRT4_YEAST] Involved in mRNA turnover and ribosome assembly. [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.[16] [17] [18] [NOG2_YEAST] GTPase that associates with pre-60S ribosomal subunits in the nucleolus and is required for their nuclear export and maturation.[19] [RL4A_YEAST] Participates in the regulation of the accumulation of its own mRNA.[20] [RL37A_YEAST] Binds to the 23S rRNA (By similarity). [BUD20_YEAST] Involved in positioning the proximal bud pole signal.[21] [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.[22] [23] [24] [25] [26] [27] [NOP15_YEAST] Involved in the biogenesis of the 60S ribosomal subunit. Required for pre-rRNA processing and cytokinesis. Associates with the precursors of the 25S and 5.8S rRNAs.[28] [29] [RLP24_YEAST] Involved in the biogenesis of the 60S ribosomal subunit. Ensures the docking of NOG1 to pre-60S particles.[30] [RL5_YEAST] Binds 5S RNA and is required for 60S subunit assembly. [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.[31] [32] [NUG1_YEAST] GTPase required for 60S ribosomal subunit export to the cytoplasm.[33] [NOP53_YEAST] Late-acting factor in the nuclear maturation of 60S ribosomal subunits, which is required for normal acquisition of export competence. Required for the export of the large subunit. Acts to stimulate the RNase activity of the exosome complex, and may recruit the exosome to 7S pre-rRNA for processing. Associates with numerous RNAs including the 27S and 7S pre-rRNAs and the box H/ACA snoRNA snR37. Also interacts (via N-terminal region) with the mature 25S rRNA and the mature 5.8S rRNA.[34] [35] [36] [37]
Publication Abstract from PubMed
Ribosome biogenesis is a highly complex process in eukaryotes, involving temporally and spatially regulated ribosomal protein (r-protein) binding and ribosomal RNA remodelling events in the nucleolus, nucleoplasm and cytoplasm. Hundreds of assembly factors, organized into sequential functional groups, facilitate and guide the maturation process into productive assembly branches in and across different cellular compartments. However, the precise mechanisms by which these assembly factors function are largely unknown. Here we use cryo-electron microscopy to characterize the structures of yeast nucleoplasmic pre-60S particles affinity-purified using the epitope-tagged assembly factor Nog2. Our data pinpoint the locations and determine the structures of over 20 assembly factors, which are enriched in two areas: an arc region extending from the central protuberance to the polypeptide tunnel exit, and the domain including the internal transcribed spacer 2 (ITS2) that separates 5.8S and 25S ribosomal RNAs. In particular, two regulatory GTPases, Nog2 and Nog1, act as hub proteins to interact with multiple, distant assembly factors and functional ribosomal RNA elements, manifesting their critical roles in structural remodelling checkpoints and nuclear export. Moreover, our snapshots of compositionally and structurally different pre-60S intermediates provide essential mechanistic details for three major remodelling events before nuclear export: rotation of the 5S ribonucleoprotein, construction of the active centre and ITS2 removal. The rich structural information in our structures provides a framework to dissect molecular roles of diverse assembly factors in eukaryotic ribosome assembly.
Diverse roles of assembly factors revealed by structures of late nuclear pre-60S ribosomes.,Wu S, Tutuncuoglu B, Yan K, Brown H, Zhang Y, Tan D, Gamalinda M, Yuan Y, Li Z, Jakovljevic J, Ma C, Lei J, Dong MQ, Woolford JL Jr, Gao N Nature. 2016 Jun 2;534(7605):133-7. doi: 10.1038/nature17942. PMID:27251291[38]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Jager S, Strayle J, Heinemeyer W, Wolf DH. Cic1, an adaptor protein specifically linking the 26S proteasome to its substrate, the SCF component Cdc4. EMBO J. 2001 Aug 15;20(16):4423-31. PMID:11500370 doi:http://dx.doi.org/10.1093/emboj/20.16.4423
- ↑ Fatica A, Oeffinger M, Tollervey D, Bozzoni I. Cic1p/Nsa3p is required for synthesis and nuclear export of 60S ribosomal subunits. RNA. 2003 Dec;9(12):1431-6. PMID:14623999
- ↑ 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
- ↑ Dunbar DA, Dragon F, Lee SJ, Baserga SJ. A nucleolar protein related to ribosomal protein L7 is required for an early step in large ribosomal subunit biogenesis. Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13027-32. PMID:11087857 doi:http://dx.doi.org/10.1073/pnas.97.24.13027
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Harnpicharnchai P, Jakovljevic J, Horsey E, Miles T, Roman J, Rout M, Meagher D, Imai B, Guo Y, Brame CJ, Shabanowitz J, Hunt DF, Woolford JL Jr. Composition and functional characterization of yeast 66S ribosome assembly intermediates. Mol Cell. 2001 Sep;8(3):505-15. PMID:11583614
- ↑ Oeffinger M, Tollervey D. Yeast Nop15p is an RNA-binding protein required for pre-rRNA processing and cytokinesis. EMBO J. 2003 Dec 15;22(24):6573-83. PMID:14657029 doi:http://dx.doi.org/10.1093/emboj/cdg616
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Sydorskyy Y, Dilworth DJ, Halloran B, Yi EC, Makhnevych T, Wozniak RW, Aitchison JD. Nop53p is a novel nucleolar 60S ribosomal subunit biogenesis protein. Biochem J. 2005 Jun 15;388(Pt 3):819-26. PMID:15686447 doi:http://dx.doi.org/BJ20041297
- ↑ Thomson E, Tollervey D. Nop53p is required for late 60S ribosome subunit maturation and nuclear export in yeast. RNA. 2005 Aug;11(8):1215-24. PMID:16043506 doi:http://dx.doi.org/10.1261/rna.2720205
- ↑ Granato DC, Gonzales FA, Luz JS, Cassiola F, Machado-Santelli GM, Oliveira CC. Nop53p, an essential nucleolar protein that interacts with Nop17p and Nip7p, is required for pre-rRNA processing in Saccharomyces cerevisiae. FEBS J. 2005 Sep;272(17):4450-63. PMID:16128814 doi:http://dx.doi.org/10.1111/j.1742-4658.2005.04861.x
- ↑ Granato DC, Machado-Santelli GM, Oliveira CC. Nop53p interacts with 5.8S rRNA co-transcriptionally, and regulates processing of pre-rRNA by the exosome. FEBS J. 2008 Aug;275(16):4164-78. doi: 10.1111/j.1742-4658.2008.06565.x. Epub, 2008 Jul 9. PMID:18631361 doi:http://dx.doi.org/10.1111/j.1742-4658.2008.06565.x
- ↑ Wu S, Tutuncuoglu B, Yan K, Brown H, Zhang Y, Tan D, Gamalinda M, Yuan Y, Li Z, Jakovljevic J, Ma C, Lei J, Dong MQ, Woolford JL Jr, Gao N. Diverse roles of assembly factors revealed by structures of late nuclear pre-60S ribosomes. Nature. 2016 Jun 2;534(7605):133-7. doi: 10.1038/nature17942. PMID:27251291 doi:http://dx.doi.org/10.1038/nature17942
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