Dataset Information

Cooperative 2'-O-methylation of the wobble cytidine of human elongator tRNA^Met(CAT) by a nucleolar and a Cajal body-specific box C/D RNP.

ABSTRACT: Site-specific 2'-O-ribose methylation of mammalian rRNAs and RNA polymerase II-synthesized spliceosomal small nuclear RNAs (snRNAs) is mediated by small nucleolar and small Cajal body (CB)-specific box C/D ribonucleoprotein particles (RNPs) in the nucleolus and the nucleoplasmic CBs, respectively. Here, we demonstrate that 2'-O-methylation of the C34 wobble cytidine of human elongator tRNA^Met(CAT) is achieved by collaboration of a nucleolar and a CB-specific box C/D RNP carrying the SNORD97 and SCARNA97 box C/D 2'-O-methylation guide RNAs. Methylation of C34 prevents site-specific cleavage of tRNA^Met(CAT) by the stress-induced endoribonuclease angiogenin, implicating box C/D guide RNPs in controlling stress-responsive production of putative regulatory tRNA fragments.

SUBMITTER: Vitali P

PROVIDER: S-EPMC6601510 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Cooperative 2'-O-methylation of the wobble cytidine of human elongator tRNA<sup>Met</sup>(CAT) by a nucleolar and a Cajal body-specific box C/D RNP.

Vitali Patrice P Kiss Tamás T

Genes & development 20190606 13-14

Site-specific 2'-O-ribose methylation of mammalian rRNAs and RNA polymerase II-synthesized spliceosomal small nuclear RNAs (snRNAs) is mediated by small nucleolar and small Cajal body (CB)-specific box C/D ribonucleoprotein particles (RNPs) in the nucleolus and the nucleoplasmic CBs, respectively. Here, we demonstrate that 2'-O-methylation of the C34 wobble cytidine of human elongator tRNA<sup>Met</sup>(CAT) is achieved by collaboration of a nucleolar and a CB-specific box C/D RNP carrying the S ...[more]

PMID: 31171702

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Project description:The eukaryotic multisubunit Elongator complex has been shown to perform multiple functions in transcriptional elongation, histone acetylation and tRNA modification. However, the Elongator complex plays different roles in different organisms, and the underlying mechanisms remain unexplored. Moreover, the biological functions of the Elongator complex in human fungal pathogens remain unknown. In this study, we verified that the Elongator complex of the opportunistic fungal pathogen Aspergillus fumigatus consists of six subunits (Elp1-6), and the loss of any subunit results in similarly defective colony phenotypes with impaired hyphal growth and reduced conidiation. The catalytic subunit-Elp3 of the Elongator complex includes a S-adenosyl methionine binding (rSAM) domain and a lysine acetyltransferase (KAT) domain, and it plays key roles in the hyphal growth, biofilm-associated exopolysaccharide galactosaminogalactan (GAG) production, adhesion and virulence of A. fumigatus; however, Elp3 does not affect H3K14 acetylation levels in vivo. LC-MS/MS chromatograms revealed that loss of Elp3 abolished the 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U) modification of tRNA wobble uridine (U34), and the overexpression of tRNAGlnUUG and tRNAGluUUC, which normally harbor mcm5s2U modifications, mainly rescues the defects of the Δelp3 mutant, suggesting that tRNA modification rather than lysine acetyltransferase is responsible for the primary function of Elp3 in A. fumigatus. Strikingly, global proteomic comparison analyses showed significantly upregulated expression of genes related to amino acid metabolism in the Δelp3 mutant strain compared to the wild-type strain. Western blotting showed that deletion of elp3 resulted in overexpression of the amino acid starvation-responsive transcription factor CpcA, and deletion of CpcA markedly reversed the defective phenotypes of the Δelp3 mutant, including attenuated virulence. Therefore, the findings of this study demonstrate that A. fumigatus Elp3 functions as a tRNA-modifying enzyme in the regulation of growth, GAG production, adhesion and virulence by maintaining intracellular amino acid homeostasis. More broadly, our study highlights the importance of U34 tRNA modification in regulating cellular metabolic states and virulence traits of fungal pathogens.

Dataset Information

Cooperative 2'-O-methylation of the wobble cytidine of human elongator tRNA^Met(CAT) by a nucleolar and a Cajal body-specific box C/D RNP.

Publications

Cooperative 2'-O-methylation of the wobble cytidine of human elongator tRNA<sup>Met</sup>(CAT) by a nucleolar and a Cajal body-specific box C/D RNP.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Cooperative 2'-O-methylation of the wobble cytidine of human elongator tRNAMet(CAT) by a nucleolar and a Cajal body-specific box C/D RNP.

Publications

Cooperative 2'-O-methylation of the wobble cytidine of human elongator tRNA<sup>Met</sup>(CAT) by a nucleolar and a Cajal body-specific box C/D RNP.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Cooperative 2'-O-methylation of the wobble cytidine of human elongator tRNA^Met(CAT) by a nucleolar and a Cajal body-specific box C/D RNP.