TRNA senses cellular nutrient status and senescence via amino acid acylation
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ABSTRACT:
PROVIDER: PRJNA661542 | ENA |
REPOSITORIES: ENA
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Project description:We profiled the cellular tRNA charging landscape using next-generation sequencing and identified a subset of tRNA that sense nutrients. The charging levels of tRNAGln were exclusively and significantly decreased in response to amino acid starvation.
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Project description:Aminoacyl tRNA synthetases are key enzymes in protein synthesis, attaching the proper amino acid to the corresponding tRNA to make protein. However, their roles in regulating plant growth and development still remain elusive. Here we reported a rice thermo-sensitive mutant yellow leaf chlorosis3 (ylc3) with reduced chlorophyll content, altered thylakoid structure, and substantially elevated levels of free aspartate, asparagine and glutamine in leaves under low temperature condition. Map-based cloning identified that YLC3 encodes an aspartyl-tRNA synthetase which is localized in cytosol and mitochondria. In addition, quantitative proteomics analysis revealed that both nuclear and chloroplast-encoded thylakoid proteins were significantly down-regulated in the mutant. On the other hand, proteins involved in amino acid metabolism and the process of protein synthesis were up-regulated in ylc3, particularly for key enzymes that convert aspartate to asparagine. Moreover, uncharged tRNA-Asp accumulation and the phosphorylation of rice translation initiation factor eIF2α(the alpha subunit of eukaryotic translation initiation factor 2) is detected , suggesting that YLC3 regulates the homeostasis of amino acid metabolism and chloroplast thylakoid development through regulation of the protein translation and synthesis processes.
2022-02-08 | PXD031497 |
Project description:Increased proliferation and elevated levels of protein synthesis are characteristic of transformed and tumor cells. Though components of the translation machinery are often misregulated in cancers, how tRNA plays a role in cancer cells has not been explored. We compare genome-wide tRNA expression in tumorigenic versus non-tumorigenic breast cell lines, as well as tRNA expression in breast tumors versus normal breast tissues. In tumorigenic versus non-tumorigenic cell lines, nuclear-encoded tRNAs increase by up to 3-fold and mitochondrial-encoded tRNAs increase by up to 5-fold. In tumors versus normal breast tissues, both nuclear and mitochondrial-encoded tRNAs increase by up to 10-fold. This tRNA over-expression is selective and coordinates with the properties of cognate amino acids. Nuclear- and mitochondrial-encoded tRNAs exhibit distinct expression patterns, indicating that tRNAs can be used as biomarkers for breast cancer. We analyzed tRNA expression levels in 2 non-tumorigenic breast cell lines, 6 tumorigenic breast cancer cell lines, 3 normal breast tissue samples, and 9 breast tumor samples. We used a non-tumorigenic breast cell line (MCF10A) as a reference sample in all hybridizations. All data is dye-swapped.
2010-05-22 | E-GEOD-17945 | biostudies-arrayexpress
Project description:The Synthetase Sequestration Model (SSM) is a simplified translation model that considers explicitly two main steps in the process of tRNA aminoacylation: first, the tRNA is bound by the aminoacyl tRNA synthetase, and in a second step, the amino acid is attached to the tRNA. The tRNA then participates in the translation reaction, becoming deacylated as a result. The tRNA exists in states bound, charged and uncharged. In the bound state, the tRNA is bound to the synthetase but uncharged, i.e., the tRNA is sequestered by the synthetase. The model predicts how the balance between the three different tRNA states (empty, bound and charged) changes depending on aminoacyl tRNA synthetase availability.
2020-02-05 | MODEL2001080005 | BioModels
Project description:Transfer RNAs (tRNA) are quintessential in deciphering the genetic code; disseminating nucleic acid triplets into correct amino acid identity. While this decoding function is clear, an emerging theme is that tRNA abundance and functionality can powerfully impact protein production rate, folding, activity, and messenger RNA stability. Importantly, however, the expression pattern of tRNAs (in even simple systems) is obliquely known. Limited analysis suggests tRNA levels change during proliferation, differentiation, cancer, and neurodegeneration; possibly mediating changes in translation efficiency and mRNA stability. A major limitation for the field has been the ability to subject tRNA pools to high-throughput analysis as they are highly structured, modified, and of high sequence similarity. Here we present Quantitative Mature tRNA sequencing (QuantM-tRNA seq), an easily implemented high-throughput technique to monitor tRNA abundance and sequence variants (possibly due to RNA modifications). With QuantM-tRNA seq we provide a comprehensive analysis of the tRNA transcriptome from distinct mammalian tissues. We observe dramatic distinctions in isodecoder expression and likely RNA modifications between unique tissues with a particularly strong signature within the central nervous system. Remarkably, despite dramatic changes in tRNA isodecoder gene expression, the overall anticodon pool of each tRNA family is similar. These findings suggest that anticodon pools are buffered via an unknown mechanism to achieve uniform decoding throughout the body.
2020-08-04 | GSE141436 | GEO
Project description:The human genome encodes hundreds of tRNA genes but their individual contribution to the tRNA pool is not fully understood. Deep sequencing of tRNA transcripts (tRNA-Seq) can estimate tRNA abundance at single gene resolution, but tRNA structures and post-transcriptional modifications impair these analyses. Here we present a bioinformatics strategy to investigate differential tRNA gene expression and use it to compare tRNA-Seq datasets from cultured human cells and human brain. We find that sequencing caveats affect quantitation of only a subset of human tRNA genes. Unexpectedly, we detect several cases where the differences in tRNA expression among samples do not involve variations at the level of isoacceptor tRNA sets (tRNAs charged with the same amino acid but using different anticodons); but rather among tRNA genes within the same isodecoder set (tRNAs having the same anticodon sequence). Because isodecoder tRNAs are functionally equal in terms of genetic translation, their differential expression may be related to non-canonical tRNA functions. We show that several instances of differential tRNA gene expression result in changes in the abundance of tRNA-derived fragments (tRFs) but not of mature tRNAs. Examples of differentially expressed tRFs include: PIWI-associated RNAs, tRFs present in tissue samples but not in cells cultured in vitro, and somatic tissue-specific tRFs. Our data support that differential expression of tRNA genes regulate non-canonical tRNA functions performed by tRFs.
2019-04-17 | GSE114904 | GEO
Project description:mRNA degradation is a critical aspect of gene expression which dictates mRNA steady-state levels in conjunction with transcription rate. Previous studies in other model organisms have demonstrated that enrichment of specific codons within the open reading frame (ORF) can influence mRNA stability, primarily by modulating translation elongation speed. Despite advancements in our understanding of mRNA stability regulation by microRNAs and 3'UTR-based factors in mammalian systems, the importance of other mRNA regions such as the ORF sequence on dictating cellular mRNA levels are incompletely understood. To characterize the effects of the coding sequence on mRNA decay in mammals, we analyzed mRNA stability in human and Chinese Hamster Ovary (Cricetulus griseus) cells by both global metabolic labeling and single-gene mRNA reporter transcription shutoffs. In agreement with previous studies, we observed that synonymous codon usage impacts mRNA stability in mammalian cells. Unexpectedly, we also found that amino acid content is a potent determinant of mRNA stability in humans and other mammalian species. Codon and amino acid effects on decay correlate with tRNA levels measured by tRNA-Seq or intracellular amino acid levels measured by HPLC, respectively. These results suggest that both tRNA and amino acid levels have complementary effects on regulation of mRNA stability in mammals, hinting at the possibility of dynamic control of mRNA levels via altered tRNA or amino acid levels.
2020-03-01 | GSE138292 | GEO
Project description:Measurements of cellular tRNA abundance are hampered by pervasive blocks to cDNA synthesis at modified nucleosides and the extensive similarity among tRNA genes. We overcome these limitations with modification-induced misincorporation tRNA sequencing (mim-tRNAseq), which combines a workflow for full-length cDNA library construction from mature tRNA with a simple-to-use computational analysis toolkit. Our method accurately captures tRNA abundance and modification status in multiple eukaryotes and is applicable to any organism with a known genome.
2021-02-12 | GSE152621 | GEO
Project description:An adaptive feature of malaria-causing parasites is the digestion of host hemoglobin (HB) to acquire amino acids (AAs). Here we describe a link between nutrient availability and translation dependent regulation of gene expression as an adaptive strategy. We show that tRNA expression in Plasmodium falciparum does not match the decoding need expected for optimal translation. A subset of tRNAs decoding AAs that are insufficiently provided by HB are lowly expressed, wherein the abundance of a protein-coding transcript is negatively correlated with the decoding requirement of these tRNAs. Proliferation-related genes have evolved a high requirement of these tRNAs, thereby proliferation can be modulated by repressing protein synthesis of these genes during nutrient stress. We conclude that the parasite modulates translation elongation by maintaining a discordant tRNA profile to exploit variations in AA-composition among genes as an adaptation strategy. This study exemplifies metabolic adaptation as an important driving force for protein evolution.
2024-10-09 | GSE278976 | GEO
Project description:In addition to acetylation, histones are modified by a series of competing longer chain acylations. Most of these acylation marks are enriched and co-exist with acetylation on active gene regulatory elements. Their seemingly redundant functions have hindered the understanding of histone acylations’ specific roles. Here, by using an acute lymphoblastic leukaemia (ALL) cell model and blasts from B-ALL patients, we demonstrate a role for mitochondrial activity in controlling histone acylation/acetylation ratio, especially at H4K5. An increase of the crotonylation and butyrylation over acetylation on H4K5 weakens BRD4-chromatin interaction and increases BRD4 nuclear mobility and availability for binding transcription start site associated nucleosome free regions of active genes. Our data suggest that, with regard to BRD4 dynamics, histone acylations including acetylation, should be considered collectively. A metabolism dependant control of the histone acetylation/longer chain acylation(s) ratio could constitute a common mechanism regulating bromodomain factors’ “reservoir” pool, availability and functional genomic distribution.
2021-06-25 | GSE164031 | GEO