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A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription [CLIP-seq]

ABSTRACT: A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription [CLIP-seq]

PROVIDER: PRJNA699896 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13643078_1.fastq.gz	Fastqsanger.gz
	SRR13643078_2.fastq.gz	Fastqsanger.gz
	SRR13643079_1.fastq.gz	Fastqsanger.gz
	SRR13643079_2.fastq.gz	Fastqsanger.gz

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A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription [CLIP-seq]

Project description:Since numerous RNAs and RBPs prevalently localize to active chromatin regions, many RNA binding proteins (RBPs) may be potential transcriptional regulators. RBPs are generally thought to regulate transcription via noncoding RNAs. Here, we describe a distinct, dual mechanism of transcriptional regulation by the previously uncharacterized tRNA-modifying enzyme, hTrmt13. On one hand, hTrmt13 acts in the cytoplasm to catalyze 2'-O-methylation of tRNAs, thus regulating translation in a manner depending on its tRNA-modification activity. On the other hand, nucleus-localized hTrmt13 directly binds DNA as a transcriptional co-activator of key epithelial mesenchymal transition factors, thereby promoting cell migration independent of tRNA-modification activity. These dual functions of hTrmt13 are mutually exclusive, as it can bind either DNA or tRNA through its CHHC zinc finger domain. Finally, we find that hTrmt13 expression is tightly associated with poor prognosis and survival in diverse cancer patients. Our discovery of the noncatalytic roles of an RNA modifying enzyme provides a new perspective for understanding epitranscriptomic regulation.

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A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription [RNA-seq]

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A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription [ChIP-seq]

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A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription

Project description:A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription

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A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription [RNA-seq]

Project description:A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription [RNA-seq]

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A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription [ChIP-seq]

Project description:A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription [ChIP-seq]

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METTL6 is a tRNA m3C methyltransferase that regulates translation and cell proliferation

Project description:Here, we identified METTL6 as a bona fide tRNA methyltransferase, catalysing the formation of 3-methylcytidine (m3C) at C32 of specific serine tRNA isoacceptors. Accordingly, deletion of METTL6 in mouse stem cells results in changes in ribosome occupancy and RNA levels, as well as a spontaneous loss of pluripotency

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A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription

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The dual methyltransferase METTL13 targets N-terminus and Lys55 of eEF1A and regulates codon-specific translation rates

Project description:Eukaryotic elongation factor 1 alpha (eEF1A) delivers aminoacyl-tRNA to the ribosome and thereby plays a key role in protein synthesis. Human eEF1A is post-translationally methylated on several lysine residues as well as on the N-terminus and until recently the responsible methyltransferases were largely elusive. Using mass spectrometry based screens, gene targeted cells and in vitro enzymology we identify the human methyltransferase like proteins 13 (METTL13), which contains two distinct methyltransferase domains, as an enzyme catalyzing both dimethylation of Lys55 and trimethylation of the N-terminus of eEF1A. Moreover, through ribosome profiling we demonstrate that loss of METTL13 function alters translation dynamics and results in changed translation rate of specific codons. In line with the established descriptive nomenclature for this type of enzymes we suggest that METTL13 is redubbed eEF1A dual methyltransferase (eEF1A-DMT / EEF1ADMT).

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A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-10-29 | GSE166278 | GEO