Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Copy number variation in tRNA isodecoders impairs mammalian development and balanced translation

ABSTRACT: The number of tRNA isodecoder genes has increased dramatically in mammals, but the specific molecular and physiological reasons for this expansion remain elusive. To address this fundamental question we used CRISPR editing to knockout the seven-membered phenylalanine tRNA gene family in mice, both individually and combinatorially. Using ATAC-seq, RNA-seq and proteomics we observed distinct molecular consequences of individual tRNA deletions. We show that tRNA-Phe-1-1 is required for neuronal function and its loss is partially compensated by increased expression of other tRNAs but results in mistranslation. In contrast, the other tRNA-Phe isodecoders compensate for the loss of each of the remaining six tRNA-Phe genes. In the tRNA-Phe gene family, the expression of at least four tRNA-Phe isodecoders is required for embryonic development and survival. The loss of tRNA-Phe-1-1 and any other three tRNA-Phe genes causes embryonic lethality indicating that tRNA-Phe-1-1 is most important for development and survival. Our results reveal that the multi-copy configuration of tRNA isodecoder genes is required to buffer translation and viability in mammals.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain, Liver

SUBMITTER: Timothy McCubbin

LAB HEAD: Aleksandra Filipovska

PROVIDER: PXD029684 | Pride | 2023-04-19

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	20200512_T4_009.raw	Raw
	20200512_T4_012.raw	Raw
	20200512_T4_015.raw	Raw
	20200512_T4_018.raw	Raw
	20200512_T4_024.raw	Raw

Items per page:

1 - 5 of 43

Similar Datasets

Genome-wide gene expression to dibenzofuran in Sphingomonas wittichii RW1

Project description:Sphingomonas wittichii RW1 is a bacterium isolated for its ability to degrade the toxic polyaromatic hydrocarbon dibenzofuran (dbf) and its polychlorinated derivatives. Its genome consists of a chromosome and two plasmids, encoding for more than 5300 genes. We studied genome-wide expression of strain RW1 to dbf in three different experimental setups, including both batch cultures and chemostats, comparing in all cases to the transcriptome of cells grown on phenylalanine as carbon source. A short exposure to DBF in chemostat or in batch, provoked the up-regulation of the ECF sigma 24, catalases, peroxiredoxins, chaperones, an aquaporin, several OmpA domain-containing proteins and the down-regulation of genes involved in TCA cycle, oxidative phosphorylation, amino acid metabolism and ribosomal proteins. When growing strain RW1 on DBF, genes known to be involved in DBF degradation were induced 2 to 4 fold. Additionally, two cluster of genes, putatively participating in the gentisate and meta-cleavage branches of the DBF degradation pathway, were induced from 12 to 19 fold. Three experiments are summarized here. 1. Compares the response of exponentially growing S.wittichii RW1 cells on phenylalanine (Phe), washed and resuspended in Phe for 30 min, with that of cells resuspended in DBF medium for 30 min (Phe1_shock, DBF1_schock, etc.). 2. Compares response of RW1 cells grown in batch medium with Phe or DBF as sole carbon and energy source, and harvested in exponential phase (Phe1_long, DBF1_long, etc. triplicates). 3. Comparison of transcriptome of RW1 cells grown continuously in chemostat on phenylalanine as carbon-limited substrate, with cells that have experienced instant exposure to phenylalanine plus DBF. This is done by pulsing DBF to maximum solubility and a simultaneous change in feed medium to Phe+ DBF. Samples before transition (Phe ctrl1-chem, etc. quadruplates), after 30 min (DBF 30m1-chem, etc), 1 h, 2 h and 6 h (DBF6h1-chem, etc.).

2012-04-17 | E-GEOD-37328 | biostudies-arrayexpress

Copy number variation in tRNA isodecoder genes impairs mammalian development and balanced translation (RNA-seq)

Project description:The number of tRNA isodecoders has increased dramatically in mammals, but the specific molecular and physiological reasons for this expansion remain elusive. To address this fundamental question we used CRISPR editing to knockout the seven-membered phenylalanine tRNA gene family in mice, both individually and combinatorially. Using ATAC-Seq, RNA-seq and proteomics we observed distinct molecular consequences of individual tRNA deletions. We show that tRNA-Phe-1-1 is required for neuronal function and its loss is partially compensated by increased expression of other tRNAs but results in mistranslation. In contrast, the other tRNA-Phe isodecoder genes buffer the loss of each of the remaining six tRNA-Phe genes. In the tRNA-Phe gene family, the expression of at least six tRNA-Phe alleles is required for embryonic viability and tRNA-Phe-1-1 is most important for development and survival. Our results reveal that the multi-copy configuration of tRNA genes is required to buffer translation and viability in mammals.

2023-03-05 | GSE223662 | GEO

Copy number variation in tRNA isodecoder genes impairs mammalian development and balanced translation [ATAC-seq]

2023-03-05 | GSE200783 | GEO

Identification of tRNA sequences in Lactococcus lactis

Project description:we report the identification and sequences of the tRNAome of industrially relevant microorganism Lactococcus lactis Three Next Generation sequencing runs annotated as S1, S2 and S3 were performed. Cells were harvested at exponential phase and tRNA was isolated. S1 and S2 were spiked with Phe-tRNAGAA from yeast and Lys-tRNAUUU from E. coli prior to cell lysis. S3 was spiked with Phe-tRNAGAA from yeast and Lys-tRNAUUU from E. coli before the library preparation to estimate the possible loss of tRNA in the extraction process.

2014-07-29 | E-GEOD-55392 | biostudies-arrayexpress

Proteomics analysis of humulene-producing yeast integrated with a low temeprature-inducible GAL circuit for pathway induction

Project description:We analysed the proteome of two humulene-producing yeast strains under normal temperature (30 °C) cultivation condition and low temperature (25 °C) cultivation condition. In these two humulene-producing yeast strains, HUM401RU (control strain) and CI-HUM401RU (low-temperature-inducible strain), the mevalonate pathway genes and the humulene synthase gene are controlled by different galactose-inducible (GAL) promoters. For CI-HUM401RU, a low-temperature-inducible GAL circuit has been introduced to enable induction of pathway genes at 25 °C. For the control strain, HUM401RU, a tetracycline-inducible promoter is used to control GAL80, so that the pathway genes can be auto-induced after glucose depleted during the cultivation. We in total submitted 12 samples which can be devided into four groups: (1) HUM401RU, 25 °C, 24h; (2) CI-HUM401RU, 30 °C, 24h; (3) CI-HUM401RU, 25 °C, 24 h; (4) CI-HUM401RU, 25 °C, 48 h. Each group has three bilogical replites.

2024-08-10 | PXD047054 | Pride

Liquid C1 fermentation differential proteomic analysis of Eubacterium limosum

Project description:Some acetogenic bacteria, such as Eubacterium limosum, have the native ability to consume liquid C1 feedstocks, such as formate and methanol, as the sole substrate for growth. Due to high energy efficiency, and compatibility with existing infrastructure, this has sparked interest in the biotechnology industry. Previously, we reported limitations of this metabolism in batch fermentation. Here we undertook chemostat differential analysis to highlight key features and bottlenecks of metabolism. Our work serves as a reference dataset to advance understanding of liquid C1 metabolism in acetogens.

2023-04-13 | PXD040283 | Pride

Genome-wide methylation profile of mitochondrial DNA across bovine preimplantation development

Project description:This study characterized variations in the methylation profile of mitochondrial DNA (mtDNA) during initial bovine embryo development and correlated the presence of methylation with mtDNA transcription. Bovine oocytes were obtained from abattoir ovaries and submitted to in vitro culture procedures. Oocytes and embryos were collected at various stages (immature oocyte, IM; mature oocyte, MII; zygote, ZY; 4-cells, 4C; 16-cells, 16C and blastocysts, BL). Total DNA (including mtDNA) was used for Whole Genome Enzymatic Methyl Sequencing and for quantification of mtDNA copy number. Extracted RNA was used for quantification of mitochondrial transcripts (ND6, CYTB, tRNA-Phe and tRNA-Gln) using Droplet Digital PCR. The number of mtDNA copies per oocyte/embryo was found to be similar, while methylation levels in mtDNA varied among stages. Higher total methylation levels were found mainly at 4C and 16C. In specific gene regions, higher methylation levels were also observed at 4C and 16C (ND6, CYTB and tRNA-Phe), as well as an inverse correlation with the quantity of transcripts for these regions. This is a first description of epigenetic changes occurring in mtDNA during early embryonic development. Our results indicate that methylation might regulate the mtDNA transcription at a local level, particularly around the time of embryonic genome activation.

2024-04-24 | GSE230476 | GEO

Circulating tRNA-derived small RNAs (tsRNAs) signature for the diagnosis and prognosis of breast cancer

Project description:Liquid biopsy is noninvasive and convenient to detect cancer-derived materials in blood or other body fluids. The aim of this study was to identify tRNA-derived small RNAs (tsRNAs) in plasma that could distinguish patients with breast cancer (BC) from healthy controls. Basing on high-throughput sequencing, 15 significantly upregulated tsRNAs were selected and assessed in cell supernatants and cell lines. 6 tsRNAs were identified and verified in a large cohort of 120 patients with BC and 112 healthy controls. tRF-Arg-CCT-017, tRF-Gly-CCC-001 and tiRNA-Phe-GAA-003 could serve as novel diagnostic biomarkers. Meanwhile, tRF-Arg-CCT-017 and tiRNA-Phe-GAA-003 could also act as prognostic biomarkers. Target genes of these tsRNAs were related to the development of cancer. These results suggest that specific tsRNAs in plasma might serve as diagnostic and prognostic biomarkers of BC.

2020-10-08 | GSE158945 | GEO

On the mechanism and origin of isoleucyl-tRNA synthetase editing against norvaline

Project description:Aminoacyl-tRNA synthetases (aaRSs), the enzymes responsible for coupling tRNAs to their cognate amino acids, minimize translational errors by intrinsic hydrolytic editing. Here, we compared the propensity of norvaline (Nva), a linear amino acid not coded for protein synthesis, to the proteinogenic, branched valine (Val) to mistranslate isoleucine (Ile) in proteins. We show that in the synthetic site of isoleucyl-tRNA synthetase (IleRS), aminoacylation and pre-transfer editing with Nva and Val occur at similar rates. Post-transfer editing was, however, more efficient with Nva as IleRS misaminoacylates Nva-tRNAIle at slower rate than Val-tRNAIle. Accordingly, an Escherichia coli strain lacking IleRS post-transfer editing misincorporated Nva and Val in the proteome to a similar extent and at the same Ile positions. However, Nva mistranslation inflicted higher toxicity than Val, in agreement with IleRS post-transfer editing domain being optimized for hydrolysis of Nva-tRNAIle. Furthermore, we found that the evolutionary related IleRS, leucyl- and valyl-tRNA synthetases (I/L/VRSs), all efficiently hydrolyze Nva-tRNAs even when editing of Nva seems redundant. Thus, we hypothesize that editing of Nva-tRNAs had already existed in the last common ancestor of I/L/VRSs, and that the editing domain of I/L/VRSs had primarily evolved to prevent infiltration of Nva into modern proteins.

2019-01-28 | PXD011051 | Pride

Formation and persistence of polyglutamine aggregates in mistranslating cells

Project description:In neurodegenerative diseases, including pathologies with well-known causative alleles, genetic factors that modify severity or age of onset are not entirely understood. We recently documented the unexpected prevalence of transfer RNA (tRNA) mutants in the human population, including variants that cause amino acid mis-incorporation. We hypothesized that a mistranslating tRNA will exacerbate toxicity and modify the molecular pathology of disease-causing alleles and investigated the combinatorial effects of tRNA variants in cellular models of Huntington’s disease. This dataset represents MS/MS data confirming Phenylaline to Serine amino acid misincorporation events caused by the tRNA-Ser G35A variant described in our study. The wildtype (WT) or mistranslating tRNA (VAR) were expressed in murine N2a cells along with mCherry protein. We affinity purified the mCherry protein to search for Ser misincorporation events at Phe codons.

2022-02-17 | PXD027837 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data