| Structural highlights
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Function
[NOG1_YEAST] Involved in the biogenesis of the 60S ribosomal subunit.[1] [RL4A_YEAST] Participates in the regulation of the accumulation of its own mRNA.[2] [RPF1_YEAST] Essential protein. Required for biogenesis of the 60S ribosomal subunit.[3] [4] [RL37A_YEAST] Binds to the 23S rRNA (By similarity). [HAS1_YEAST] ATP-dependent RNA helicase involved in 40S ribosomal subunit biogenesis. Required for the processing and cleavage of 35S pre-rRNA at sites A0, A1, and A2, leading to mature 18S rRNA.[5] [6] [7] [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.[8] [9] [10] [11] [12] [13] [RL36B_YEAST] Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules. The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain. The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel.[14] [NUG1_YEAST] GTPase required for 60S ribosomal subunit export to the cytoplasm.[15] [RLP24_YEAST] Involved in the biogenesis of the 60S ribosomal subunit. Ensures the docking of NOG1 to pre-60S particles.[16] [PESC_YEAS7] 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] [MRT4_YEAST] Involved in mRNA turnover and ribosome assembly. [BRX1_YEAST] Required for biogenesis of the 60S ribosomal subunit.[17] [ERB1_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_03027][18] [19] [MAK16_YEAST] Its role might be as part of the apparatus concerned with the nuclear events of the cell cycle.[20] [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.[21] [22] [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.[23] [24] [NOP16_YEAST] Involved in the biogenesis of the 60S ribosomal subunit.[25] [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.[26] [27] [EBP2_YEAST] Required for the processing of the 27S pre-rRNA. Probably involved in the step of the processing of the 27 SA precursor into the 27 SB intermediate.[28] [29] [RRP1_YEAST] Required for 27S rRNA processing to 25S and 5.8S. [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.[30] [NSA1_YEAST] Involved in the biogenesis of the 60S ribosomal subunit.[31]
Publication Abstract from PubMed
Eukaryotic 60S ribosomal subunits are comprised of three rRNAs and approximately 50 ribosomal proteins. The initial steps of their formation take place in the nucleolus, but, owing to a lack of structural information, this process is poorly understood. Using cryo-EM, we solved structures of early 60S biogenesis intermediates at 3.3 A to 4.5 A resolution, thereby providing insights into their sequential folding and assembly pathway. Besides revealing distinct immature rRNA conformations, we map 25 assembly factors in six different assembly states. Notably, the Nsa1-Rrp1-Rpf1-Mak16 module stabilizes the solvent side of the 60S subunit, and the Erb1-Ytm1-Nop7 complex organizes and connects through Erb1's meandering N-terminal extension, eight assembly factors, three ribosomal proteins, and three 25S rRNA domains. Our structural snapshots reveal the order of integration and compaction of the six major 60S domains within early nucleolar 60S particles developing stepwise from the solvent side around the exit tunnel to the central protuberance.
Visualizing the Assembly Pathway of Nucleolar Pre-60S Ribosomes.,Kater L, Thoms M, Barrio-Garcia C, Cheng J, Ismail S, Ahmed YL, Bange G, Kressler D, Berninghausen O, Sinning I, Hurt E, Beckmann R Cell. 2017 Dec 14;171(7):1599-1610.e14. doi: 10.1016/j.cell.2017.11.039. PMID:29245012[32]
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
- ↑ 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
- ↑ Wehner KA, Baserga SJ. The sigma(70)-like motif: a eukaryotic RNA binding domain unique to a superfamily of proteins required for ribosome biogenesis. Mol Cell. 2002 Feb;9(2):329-39. PMID:11864606
- ↑ 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
- ↑ Emery B, de la Cruz J, Rocak S, Deloche O, Linder P. Has1p, a member of the DEAD-box family, is required for 40S ribosomal subunit biogenesis in Saccharomyces cerevisiae. Mol Microbiol. 2004 Apr;52(1):141-58. doi: 10.1111/j.1365-2958.2003.03973.x. PMID:15049817 doi:http://dx.doi.org/10.1111/j.1365-2958.2003.03973.x
- ↑ Mnaimneh S, Davierwala AP, Haynes J, Moffat J, Peng WT, Zhang W, Yang X, Pootoolal J, Chua G, Lopez A, Trochesset M, Morse D, Krogan NJ, Hiley SL, Li Z, Morris Q, Grigull J, Mitsakakis N, Roberts CJ, Greenblatt JF, Boone C, Kaiser CA, Andrews BJ, Hughes TR. Exploration of essential gene functions via titratable promoter alleles. Cell. 2004 Jul 9;118(1):31-44. PMID:15242642 doi:10.1016/j.cell.2004.06.013
- ↑ Rocak S, Emery B, Tanner NK, Linder P. Characterization of the ATPase and unwinding activities of the yeast DEAD-box protein Has1p and the analysis of the roles of the conserved motifs. Nucleic Acids Res. 2005 Feb 17;33(3):999-1009. doi: 10.1093/nar/gki244. Print, 2005. PMID:15718299 doi:http://dx.doi.org/10.1093/nar/gki244
- ↑ 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
- ↑ Ben-Shem A, Garreau de Loubresse N, Melnikov S, Jenner L, Yusupova G, Yusupov M. The structure of the eukaryotic ribosome at 3.0 A resolution. Science. 2011 Dec 16;334(6062):1524-9. Epub 2011 Nov 17. PMID:22096102 doi:10.1126/science.1212642
- ↑ 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
- ↑ 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
- ↑ Kaser A, Bogengruber E, Hallegger M, Doppler E, Lepperdinger G, Jantsch M, Breitenbach M, Kreil G. Brix from xenopus laevis and brx1p from yeast define a new family of proteins involved in the biogenesis of large ribosomal subunits. Biol Chem. 2001 Dec;382(12):1637-47. doi: 10.1515/BC.2001.199. PMID:11843177 doi:http://dx.doi.org/10.1515/BC.2001.199
- ↑ Pestov DG, Stockelman MG, Strezoska Z, Lau LF. ERB1, the yeast homolog of mammalian Bop1, is an essential gene required for maturation of the 25S and 5.8S ribosomal RNAs. Nucleic Acids Res. 2001 Sep 1;29(17):3621-30. PMID:11522832
- ↑ 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
- ↑ Wickner RB. Host function of MAK16: G1 arrest by a mak16 mutant of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6007-11. PMID:3045810
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Huber MD, Dworet JH, Shire K, Frappier L, McAlear MA. The budding yeast homolog of the human EBNA1-binding protein 2 (Ebp2p) is an essential nucleolar protein required for pre-rRNA processing. J Biol Chem. 2000 Sep 15;275(37):28764-73. doi: 10.1074/jbc.M000594200. PMID:10849420 doi:http://dx.doi.org/10.1074/jbc.M000594200
- ↑ Tsujii R, Miyoshi K, Tsuno A, Matsui Y, Toh-e A, Miyakawa T, Mizuta K. Ebp2p, yeast homologue of a human protein that interacts with Epstein-Barr virus nuclear antigen 1, is required for pre-rRNA processing and ribosomal subunit assembly. Genes Cells. 2000 Jul;5(7):543-53. PMID:10947841
- ↑ 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
- ↑ 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
- ↑ Kater L, Thoms M, Barrio-Garcia C, Cheng J, Ismail S, Ahmed YL, Bange G, Kressler D, Berninghausen O, Sinning I, Hurt E, Beckmann R. Visualizing the Assembly Pathway of Nucleolar Pre-60S Ribosomes. Cell. 2017 Dec 14;171(7):1599-1610.e14. doi: 10.1016/j.cell.2017.11.039. PMID:29245012 doi:http://dx.doi.org/10.1016/j.cell.2017.11.039
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