| Structural highlights
Function
[TR112_YEAST] Together with MTQ2, required for the methylation of eRF1 on 'Gln-182'. Together with TRM11, required for the formation of 2-methylguanosine at position 10 in tRNA. Probably has additional functions.[1] [2] [BUD23_YEAST] S-adenosyl-L-methionine-dependent methyltransferase that specifically methylates the N(7) position of guanine 1575 (m7G1575) in 18S rRNA. Requires the methyltransferase adapter protein TRM112 for full rRNA methyltransferase activity. Important for biogenesis end export of the 40S ribosomal subunit independent on its methyltransferase activity. Required for efficient cleavage of the primary 35S precursor rRNA at site A2. Involved in positioning the proximal bud pole signal.[3] [4] [5] [6] [7] [8]
Publication Abstract from PubMed
The eukaryotic small ribosomal subunit carries only four ribosomal (r) RNA methylated bases, all close to important functional sites. N7-methylguanosine (m7G) introduced at position 1575 on 18S rRNA by Bud23-Trm112 is at a ridge forming a steric block between P- and E-site tRNAs. Here we report atomic resolution structures of Bud23-Trm112 in the apo and S-adenosyl-l-methionine (SAM)-bound forms. Bud23 and Trm112 interact through formation of a beta-zipper involving main-chain atoms, burying an important hydrophobic surface and stabilizing the complex. The structures revealed that the coactivator Trm112 undergoes an induced fit to accommodate its methyltransferase (MTase) partner. We report important structural similarity between the active sites of Bud23 and Coffea canephora xanthosine MTase, leading us to propose and validate experimentally a model for G1575 coordination. We identify Bud23 residues important for Bud23-Trm112 complex formation and recruitment to pre-ribosomes. We report that though Bud23-Trm112 binds precursor ribosomes at an early nucleolar stage, m7G methylation occurs at a late step of small subunit biogenesis, implying specifically delayed catalytic activation. Finally, we show that Bud23-Trm112 interacts directly with the box C/D snoRNA U3-associated DEAH RNA helicase Dhr1 supposedly involved in central pseudoknot formation; this suggests that Bud23-Trm112 might also contribute to controlling formation of this irreversible and dramatic structural reorganization essential to overall folding of small subunit rRNA. Our study contributes important new elements to our understanding of key molecular aspects of human ribosomopathy syndromes associated with WBSCR22 (human Bud23) malfunction.
Structural and functional studies of Bud23-Trm112 reveal 18S rRNA N7-G1575 methylation occurs on late 40S precursor ribosomes.,Letoquart J, Huvelle E, Wacheul L, Bourgeois G, Zorbas C, Graille M, Heurgue-Hamard V, Lafontaine DL Proc Natl Acad Sci U S A. 2014 Dec 8. pii: 201413089. PMID:25489090[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Purushothaman SK, Bujnicki JM, Grosjean H, Lapeyre B. Trm11p and Trm112p are both required for the formation of 2-methylguanosine at position 10 in yeast tRNA. Mol Cell Biol. 2005 Jun;25(11):4359-70. PMID:15899842 doi:http://dx.doi.org/25/11/4359
- ↑ Heurgue-Hamard V, Graille M, Scrima N, Ulryck N, Champ S, van Tilbeurgh H, Buckingham RH. The zinc finger protein Ynr046w is plurifunctional and a component of the eRF1 methyltransferase in yeast. J Biol Chem. 2006 Nov 24;281(47):36140-8. Epub 2006 Sep 28. PMID:17008308 doi:10.1074/jbc.M608571200
- ↑ 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
- ↑ White J, Li Z, Sardana R, Bujnicki JM, Marcotte EM, Johnson AW. Bud23 methylates G1575 of 18S rRNA and is required for efficient nuclear export of pre-40S subunits. Mol Cell Biol. 2008 May;28(10):3151-61. doi: 10.1128/MCB.01674-07. Epub 2008 Mar , 10. PMID:18332120 doi:http://dx.doi.org/10.1128/MCB.01674-07
- ↑ Figaro S, Wacheul L, Schillewaert S, Graille M, Huvelle E, Mongeard R, Zorbas C, Lafontaine DL, Heurgue-Hamard V. Trm112 is required for Bud23-mediated methylation of the 18S rRNA at position G1575. Mol Cell Biol. 2012 Jun;32(12):2254-67. doi: 10.1128/MCB.06623-11. Epub 2012 Apr , 9. PMID:22493060 doi:http://dx.doi.org/10.1128/MCB.06623-11
- ↑ Sardana R, Johnson AW. The methyltransferase adaptor protein Trm112 is involved in biogenesis of both ribosomal subunits. Mol Biol Cell. 2012 Nov;23(21):4313-22. doi: 10.1091/mbc.E12-05-0370. Epub 2012, Sep 5. PMID:22956767 doi:http://dx.doi.org/10.1091/mbc.E12-05-0370
- ↑ Sardana R, White JP, Johnson AW. The rRNA methyltransferase Bud23 shows functional interaction with components of the SSU processome and RNase MRP. RNA. 2013 Jun;19(6):828-40. doi: 10.1261/rna.037671.112. Epub 2013 Apr 19. PMID:23604635 doi:http://dx.doi.org/10.1261/rna.037671.112
- ↑ Sardana R, Zhu J, Gill M, Johnson AW. Physical and functional interaction between the methyltransferase Bud23 and the essential DEAH-box RNA helicase Ecm16. Mol Cell Biol. 2014 Jun;34(12):2208-20. doi: 10.1128/MCB.01656-13. Epub 2014 Apr , 7. PMID:24710271 doi:http://dx.doi.org/10.1128/MCB.01656-13
- ↑ Letoquart J, Huvelle E, Wacheul L, Bourgeois G, Zorbas C, Graille M, Heurgue-Hamard V, Lafontaine DL. Structural and functional studies of Bud23-Trm112 reveal 18S rRNA N7-G1575 methylation occurs on late 40S precursor ribosomes. Proc Natl Acad Sci U S A. 2014 Dec 8. pii: 201413089. PMID:25489090 doi:http://dx.doi.org/10.1073/pnas.1413089111
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