Transfer RNA Methytransferases and Their Corresponding Modifications in Budding Yeast and Humans: Activities, Predications, and Potential Roles in Human Health

Towns, William L.; Begley, Thomas J.

doi:10.1089/dna.2011.1437

Cited by 91 publications

(85 citation statements)

References 110 publications

(121 reference statements)

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“…Trm112 activates not only the tRNA methyltransferase Trm9, but also the methylase catalytic subunit Mtq2 (in eukaryotes, the Mtq2-Trm112 holoenzyme methylates the glutamine of an essential GGQ motif at class I translation termination factors) and Trm11 (the heterodimer introduces in this case the m 2 G 10 modification at some tRNAs) (33,34). Furthermore, Trm112 can also form a complex with the methylase Bud23, which modifies the 18S rRNA subunit, but only with stabilization purposes (34).…”

Section: Discussionmentioning

confidence: 99%

Genome-wide Screening of Regulators of Catalase Expression

Garcia¹,

Dedo²,

Ayté

et al. 2016

Journal of Biological Chemistry

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In response to environmental cues, the mitogen-activated protein kinase Sty1-driven signaling cascade activates hundreds of genes to induce a robust anti-stress cellular response in fission yeast. Thus, upon stress imposition Sty1 transiently accumulates in the nucleus where it up-regulates transcription through the Atf1 transcription factor. Several regulators of transcription and translation have been identified as important to mount an integral response to oxidative stress, such as the SptAda-Gcn5-acetyl transferase or Elongator complexes, respectively. With the aim of identifying new regulators of this massive gene expression program, we have used a GFP-based protein reporter and screened a fission yeast deletion collection using flow cytometry. We find that the levels of catalase fused to GFP, both before and after a threat of peroxides, are altered in hundreds of strains lacking components of chromatin modifiers, transcription complexes, and modulators of translation. Thus, the transcription elongation complex Paf1, the histone methylase Set1-COMPASS, and the translation-related Trm112 dimers are all involved in full expression of Ctt1-GFP and in wild-type tolerance to peroxides.Cells adapt to changing environments by activating signaling pathways and modifying the cellular gene expression programs. Often, those signals are stressful and transiently or permanently halt cell growth. In particular, reactive oxygen species such as hydrogen peroxide (H 2 O 2 ) trigger what is known as oxidative stress. In fission yeast, Ͼ550 types of transcripts are up-regulated Ͼ2-fold in response to peroxides, and the expression of up to 450 genes is down-regulated also by Ͼ2-fold (1). This severe change in the Schizosaccharomyces pombe transcriptome is ruled by the mitogen-activated protein kinase Sty1-driven signaling cascade, which becomes activated upon different stress signals such as H 2 O 2 to allow adaptation and survival.Upon activation, Sty1 accumulates in the nucleus and orchestrates this massive change in the cell gene expression program. The downstream transcription factor Atf1 is important for this response. Atf1 is phosphorylated by Sty1 in a stressdependent manner, and transcription of genes occurs. We and others have demonstrated that the SAGA 4 complex is recruited to stress genes in a Sty1-and Atf1-dependent manner (2, 3) and participate in chromatin remodeling along stress open reading frames to allow RNA polymerase II (Pol II) initiation and elongation.For this dramatic change in the gene expression program to occur, not only the Pol II transcriptional machinery but also the translation process of the newly induced stress mRNAs has to be coordinated (4) and also be robust. Thus, we recently described that mutations in Elongator components impair wild-type tolerance to peroxides, probably by decreasing the amount of proteins synthesized from the stress mRNAs (5). Elongator introduces a modification of the anticodon loop of the low copy number tRNA UUU Lys as well as in other two types of tRNAs with a urac...

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Section: Discussionmentioning

confidence: 99%

Genome-wide Screening of Regulators of Catalase Expression

Garcia¹,

Dedo²,

Ayté

et al. 2016

Journal of Biological Chemistry

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“…The biosynthesis of many tRNA modifications has been defined for S. cerevisiae, with homologs of the corresponding enzyme systems present in humans. 49 Biological pathways as complex as those associated with tRNA metabolism allow for the regulation of tRNA and modifications at many discrete levels in order to fine tune translation, particularly under conditions of stress. Indeed, there are documented cases of stress-induced regulation of tRNA from the initial transcript to translation-associated forms (Fig.…”

Section: Stress-induced Regulation Of Trnamentioning

confidence: 99%

Codon-biased translation can be regulated by wobble-base tRNA modification systems during cellular stress responses

2015

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“…However, the idea that tRNA modifications and their respective pathways can be connected with regulatory functions has recently emerged. Indeed, new roles of tRNA modifications as connectors between translation, metabolism and stress response have been recently uncovered [10][11][12][13][14][15][16][17]. It became clear that tRNA modifications are central to a global quality control of the cell integrity and that tRNA maturation pathways might be placed at the cross-road of various regulation pathways such as the response to oxidative stress or metabolite starvation [1,[19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%