Trm112p Is a 15-kDa Zinc Finger Protein Essential for the Activity of Two tRNA and One Protein Methyltransferases in Yeast

Mazauric, Marie‐Hélène; Dirick, Léon; Purushothaman, Suresh K.; Björk, Glenn R.; Lapeyre, Bruno

doi:10.1074/jbc.m110.113100

Cited by 58 publications

(94 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…17 Inactivation of the other S. cerevisiae Elongator genes encoding Elp1-Elp2p and Elp4-Elp6p displayed identical phenotypes as the elp3 null mutant including the tRNA modification defect. 17,18 This observation suggested that the Elongator complex is required for synthesis of the first step, an intermediate likely to be 5-carboxymethyluridine (cm 5 U) [19][20][21][22][23] , in formation of mcm 5 U, mcm 5 s 2 U, ncm 5 U and ncm 5 U m at U 34 in tRNA (Fig. 1).…”

Section: 15mentioning

confidence: 99%

See 1 more Smart Citation

Elongator, a conserved complex required for wobble uridine modifications in Eukaryotes

Karlsborn

Tükenmez

Mahmud³

et al. 2014

RNA Biology

109

104

View full text Add to dashboard Cite

Section: 15mentioning

confidence: 99%

“…2). [20][21][22][23]52,53 Other than being a subunit required for Trm9p activity, Trm112p is also a subunit required for the activity of 3 other methyltransferases, the tRNA methyltransferase Trm11p forming m 2 G 10 in tRNA, the ribosomal methyl transferase Bud23p methylating G1575 in 18S rRNA 54 and Mtq2p methylating the release factor eRF1.…”

mentioning

confidence: 99%

Elongator, a conserved complex required for wobble uridine modifications in Eukaryotes

Karlsborn

Tükenmez

Mahmud³

et al. 2014

RNA Biology

109

104

View full text Add to dashboard Cite

“…Trm112 is a small zinc finger protein of 15 kDa which acts as a coactivator of several class I S-adenosyl-L-methionine (SAM)-dependent MTases (15,32,36,49,58). To date, Trm112 is known to interact with, and to activate, three MTases, namely, Mtq2, Trm9, and Trm11, all related to ribosome function.…”

mentioning

confidence: 99%

Trm112 Is Required for Bud23-Mediated Methylation of the 18S rRNA at Position G1575

Figaro

Wacheul

Schillewaert

et al. 2012

Molecular and Cellular Biology

122

View full text Add to dashboard Cite

Posttranscriptional and posttranslational modification of macromolecules is known to fine-tune their functions. Trm112 is unique, acting as an activator of both tRNA and protein methyltransferases. Here we report that in Saccharomyces cerevisiae, Trm112 is required for efficient ribosome synthesis and progression through mitosis. Trm112 copurifies with pre-rRNAs and with multiple ribosome synthesis trans-acting factors, including the 18S rRNA methyltransferase Bud23. Consistent with the known mechanisms of activation of methyltransferases by Trm112, we found that Trm112 interacts directly with Bud23 in vitro and that it is required for its stability in vivo. Consequently, trm112⌬ cells are deficient for Bud23-mediated 18S rRNA methylation at position G1575 and for small ribosome subunit formation. Bud23 failure to bind nascent preribosomes activates a nucleolar surveillance pathway involving the TRAMP complexes, leading to preribosome degradation. Trm112 is thus active in rRNA, tRNA, and translation factor modification, ideally placing it at the interface between ribosome synthesis and function.A ctively growing budding yeast cells produce an average of 33 ribosomes per second, which is considerable (61). Besides the synthesis of its constituents, i.e., 79 ribosomal proteins and 4 rRNAs, ribogenesis involves a large number of so-called transacting factors, including proteins and small nucleolar RNAs (13, 56). These interact only transiently with preribosomes and are required for pre-rRNA processing (i.e., cleavages), pre-rRNA modification, and preribosome assembly and transport.Ribosome synthesis is initiated in the nucleolus, a highly dynamic specialized subcompartment of the nucleus organized around clusters of actively transcribed rRNA genes (60). There, RNA polymerase I produces a 35S/47S (in yeasts and humans, respectively) primary transcript which is processed through a complex succession of endo-and exoribonucleolytic cleavages into three of the four mature rRNAs, the 18S, 5.8S, and 25S/28S rRNAs. The fourth rRNA, 5S, is independently transcribed by RNA polymerase III. Ribosome maturation starts cotranscriptionally in the nucleolus, progresses in the nucleoplasm until preribosomes reach the nuclear pore complex, and is finalized in the cytoplasm. Cytoplasmic maturation steps consisting of pre-rRNA processing and structural reorganization result in the assembly of prominent ribosomal structures, such as the "beak" of the small subunit (SSU) and the "stalk" of the large subunit, and are a prerequisite to the acquisition of functionality (43).It is not clear how the various facets of ribosome synthesis are integrated with ribosome function. However, there is growing evidence that such coordination exists. For the small subunit, recent cryoelectron microscopy (cryo-EM) maps of late pre-40S subunits indicate that the binding of trans-acting factors literally mask functional sites, preventing premature translation initiation (57). For the large subunit, trans-acting factors that resemble ribosomal proteins (suc...

show abstract

“…Interestingly, PaOrf2 is unable to cleave its substrates when the wobble uridine methylase Trm9 (part of a complex with Trm112) is lacking (Klassen et al 2008a). Since Trm9-Trm112 catalyzes the last step of mcm 5 /mcm 5 s 2 biosynthesis (Kalhor and Clarke 2003;Mazauric et al 2010;Chen et al 2011), and trm9 mutants accumulate ncm 5 s 2 (5-carbamoylmethyl-2-thiouridine) instead of mcm 5 s 2 (Chen et al 2011), it appears that this moiety is inhibitory for PaT.…”

Section: Introductionmentioning

confidence: 99%

A fungal anticodon nuclease ribotoxin exploits a secondary cleavage site to evade tRNA repair

Meineke

Alene

Schwer

et al. 2012

RNA

View full text Add to dashboard Cite

PaOrf2 and g-toxin subunits of Pichia acaciae toxin (PaT) and Kluyveromyces lactis zymocin are tRNA anticodon nucleases. These secreted ribotoxins are assimilated by Saccharomyces cerevisiae, wherein they arrest growth by depleting specific tRNAs. Toxicity can be recapitulated by induced intracellular expression of PaOrf2 or g-toxin in S. cerevisiae. Mutational analysis of g-toxin has identified amino acids required for ribotoxicity in vivo and RNA transesterification in vitro. Here, we report that PaOrf2 residues Glu9 and His287 (putative counterparts of g-toxin Glu9 and His209) are essential for toxicity. Our results suggest a similar basis for RNA transesterification by PaOrf2 and g-toxin, despite their dissimilar primary structures and distinctive tRNA target specificities. PaOrf2 makes two sequential incisions in tRNA, the first of which occurs 39 from the mcm 5 s 2 U wobble nucleoside and depends on mcm 5 . A second incision two nucleotides upstream results in the net excision of a di-nucleotide. Expression of phage and plant tRNA repair systems can relieve PaOrf2 toxicity when tRNA cleavage is restricted to the secondary site in elp3 cells that lack the mcm 5 wobble U modification. Whereas the endogenous yeast tRNA ligase Trl1 can heal tRNA halves produced by PaOrf2 cleavage in elp3 cells, its RNA sealing activity is inadequate to complete the repair. Compatible sealing activity can be provided in trans by plant tRNA ligase. The damage-rescuing ability of tRNA repair systems is lost when PaOrf2 can break tRNA at both sites. These results highlight the logic of a two-incision mechanism of tRNA anticodon damage that evades productive repair by tRNA ligases.

show abstract

Trm112p Is a 15-kDa Zinc Finger Protein Essential for the Activity of Two tRNA and One Protein Methyltransferases in Yeast

Cited by 58 publications

References 53 publications

Elongator, a conserved complex required for wobble uridine modifications in Eukaryotes

Elongator, a conserved complex required for wobble uridine modifications in Eukaryotes

Trm112 Is Required for Bud23-Mediated Methylation of the 18S rRNA at Position G1575

A fungal anticodon nuclease ribotoxin exploits a secondary cleavage site to evade tRNA repair

Contact Info

Product

Resources

About