| Structural highlights
Function
[REI1_YEAST] Pre-60S-associated factor involved in the cytoplasmic maturation of the 60S subunit. Involved in the dissociation and recycling of other late pre-60S factors like ARX1, TIF6 and ALB1 before newly synthesized large ribosomal subunits enter translation. Cooperates with the co-chaperone JJJ1 in the release of the nuclear-export factor ARX1. May act redundantly with REH1 to directly promote a stabilizing structural rearrangement in cytoplasmic 60S subunit maturation independent on ARX1 recycling.[1] [2] [3] [4] [5] [6] [7] [LSG1_YEAST] GTPase required for the nuclear export of the 60S ribosomal subunit. Acts by mediating the release of NMD3 from the 60S ribosomal subunit after export into the cytoplasm.[8] [9] [10] [11] [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.[12] [13] [RL25_YEAST] This protein binds to a specific region on the 26S rRNA. [NMD3_YEAST] Acts as an adapter for the XPO1/CRM1-mediated export of the 60S ribosomal subunit. Unlikely to play a significant role in nonsense-mediated mRNA decay (NMD).[14] [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.[15] [16] [17] [18] [19] [20] [RL16B_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.[21] [RL5_YEAST] Binds 5S RNA and is required for 60S subunit assembly. [RL4A_YEAST] Participates in the regulation of the accumulation of its own mRNA.[22] [RL37A_YEAST] Binds to the 23S rRNA (By similarity). [PVH1_YEAST] May be directly involved in signal transduction and/or cell cycle regulation. It is necessary for maintaining growth rate or spore germination. Could show both activity toward tyrosine-protein phosphate as well as with serine-protein phosphate. [RL11A_YEAST] Binds to 5S ribosomal RNA.
Publication Abstract from PubMed
During their final maturation in the cytoplasm, pre-60S ribosomal particles are converted to translation-competent large ribosomal subunits. Here, we present the mechanism of peptidyltransferase centre (PTC) completion that explains how integration of the last ribosomal proteins is coupled to release of the nuclear export adaptor Nmd3. Single-particle cryo-EM reveals that eL40 recruitment stabilises helix 89 to form the uL16 binding site. The loading of uL16 unhooks helix 38 from Nmd3 to adopt its mature conformation. In turn, partial retraction of the L1 stalk is coupled to a conformational switch in Nmd3 that allows the uL16 P-site loop to fully accommodate into the PTC where it competes with Nmd3 for an overlapping binding site (base A2971). Our data reveal how the central functional site of the ribosome is sculpted and suggest how the formation of translation-competent 60S subunits is disrupted in leukaemia-associated ribosomopathies.
Mechanism of completion of peptidyltransferase centre assembly in eukaryotes.,Kargas V, Castro-Hartmann P, Escudero-Urquijo N, Dent K, Hilcenko C, Sailer C, Zisser G, Marques-Carvalho MJ, Pellegrino S, Wawiorka L, Freund SM, Wagstaff JL, Andreeva A, Faille A, Chen E, Stengel F, Bergler H, Warren AJ Elife. 2019 May 22;8. pii: 44904. doi: 10.7554/eLife.44904. PMID:31115337[23]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Iwase M, Toh-e A. Ybr267w is a new cytoplasmic protein belonging to the mitotic signaling network of Saccharomyces cerevisiae. Cell Struct Funct. 2004 Feb;29(1):1-15. PMID:15107529
- ↑ 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
- ↑ Lebreton A, Saveanu C, Decourty L, Rain JC, Jacquier A, Fromont-Racine M. A functional network involved in the recycling of nucleocytoplasmic pre-60S factors. J Cell Biol. 2006 May 8;173(3):349-60. Epub 2006 May 1. PMID:16651379 doi:http://dx.doi.org/jcb.200510080
- ↑ Demoinet E, Jacquier A, Lutfalla G, Fromont-Racine M. The Hsp40 chaperone Jjj1 is required for the nucleo-cytoplasmic recycling of preribosomal factors in Saccharomyces cerevisiae. RNA. 2007 Sep;13(9):1570-81. Epub 2007 Jul 24. PMID:17652132 doi:http://dx.doi.org/rna.585007
- ↑ Parnell KM, Bass BL. Functional redundancy of yeast proteins Reh1 and Rei1 in cytoplasmic 60S subunit maturation. Mol Cell Biol. 2009 Jul;29(14):4014-23. Epub 2009 May 11. PMID:19433447 doi:http://dx.doi.org/MCB.01582-08
- ↑ Meyer AE, Hoover LA, Craig EA. The cytosolic J-protein, Jjj1, and Rei1 function in the removal of the pre-60 S subunit factor Arx1. J Biol Chem. 2010 Jan 8;285(2):961-8. Epub 2009 Nov 9. PMID:19901025 doi:http://dx.doi.org/M109.038349
- ↑ Greber BJ, Boehringer D, Montellese C, Ban N. Cryo-EM structures of Arx1 and maturation factors Rei1 and Jjj1 bound to the 60S ribosomal subunit. Nat Struct Mol Biol. 2012 Nov 11. doi: 10.1038/nsmb.2425. PMID:23142985 doi:http://dx.doi.org/10.1038/nsmb.2425
- ↑ Hedges J, West M, Johnson AW. Release of the export adapter, Nmd3p, from the 60S ribosomal subunit requires Rpl10p and the cytoplasmic GTPase Lsg1p. EMBO J. 2005 Feb 9;24(3):567-79. Epub 2005 Jan 20. PMID:15660131 doi:http://dx.doi.org/7600547
- ↑ West M, Hedges JB, Chen A, Johnson AW. Defining the order in which Nmd3p and Rpl10p load onto nascent 60S ribosomal subunits. Mol Cell Biol. 2005 May;25(9):3802-13. PMID:15831484 doi:http://dx.doi.org/25/9/3802
- ↑ Hedges J, Chen YI, West M, Bussiere C, Johnson AW. Mapping the functional domains of yeast NMD3, the nuclear export adapter for the 60 S ribosomal subunit. J Biol Chem. 2006 Dec 1;281(48):36579-87. Epub 2006 Oct 2. PMID:17015443 doi:http://dx.doi.org/M606798200
- ↑ Hofer A, Bussiere C, Johnson AW. Mutational analysis of the ribosomal protein Rpl10 from yeast. J Biol Chem. 2007 Nov 9;282(45):32630-9. Epub 2007 Aug 30. PMID:17761675 doi:http://dx.doi.org/10.1074/jbc.M705057200
- ↑ 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
- ↑ Ho JH, Kallstrom G, Johnson AW. Nmd3p is a Crm1p-dependent adapter protein for nuclear export of the large ribosomal subunit. J Cell Biol. 2000 Nov 27;151(5):1057-66. PMID:11086007
- ↑ 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
- ↑ 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
- ↑ Kargas V, Castro-Hartmann P, Escudero-Urquijo N, Dent K, Hilcenko C, Sailer C, Zisser G, Marques-Carvalho MJ, Pellegrino S, Wawiorka L, Freund SM, Wagstaff JL, Andreeva A, Faille A, Chen E, Stengel F, Bergler H, Warren AJ. Mechanism of completion of peptidyltransferase centre assembly in eukaryotes. Elife. 2019 May 22;8. pii: 44904. doi: 10.7554/eLife.44904. PMID:31115337 doi:http://dx.doi.org/10.7554/eLife.44904
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