Homo sapiens strain:HepG2
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ABSTRACT:
PROVIDER: PRJNA561913 | ENA |
REPOSITORIES: ENA
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Project description:Cells respond to perturbations like inflammation by sensing changes in metabolite levels. Especially prominent is arginine, which has known connections to the inflammatory response. Here, we found that depletion of arginine during inflammation decreased levels of a nuclear form of arginyl-tRNA synthetase (ArgRS). Surprisingly, we found that nuclear ArgRS interacts and co-localizes with serine/arginine repetitive matrix protein 2 (SRRM2), a spliceosomal and nuclear speckle protein, and that decreased levels of nuclear ArgRS correlated with changes in condensate-like nuclear trafficking of SRRM2 and splice-site usage in certain genes. These splice-site usage changes cumulated in the synthesis of different protein isoforms that altered cellular metabolism and peptide presentation to immune cells. Our findings uncover a novel mechanism whereby a tRNA synthetase cognate to a key amino acid that is metabolically controlled during inflammation modulates the splicing machinery.
2023-04-14 | PXD036232 | Pride
Project description:Prior work revealed nuclear-localized aminoacyl-tRNA synthetases (aaRSs) that checked newly synthesized tRNAs for charging before export to the cytoplasm. To reveal other functions, we sought to identify nuclear proteins that interact with arginyl-tRNA synthetase (ArgRS) in the nucleus. Serine/Arginine Repetitive Matrix Protein 2 (SRRM2), which is stored with RNA splicing apparatus components in nuclear speckle condensates, was found as a consistent interaction partner that co localized with SRRM2 ArgRS in nuclear speckles. Dynamic photo-bleaching experiments showed that, consistent with condensate properties, SRRM2 has a fluctuating appearance in speckles. Knock down of ArgRS impeded SRRM2 speckle trafficking and, coincidently, altered splicing processing of pre-mRNA transcripts. Among the altered spliced variants, those of tRNA synthetase family members were prominent. Thus, nuclear ArgRS shapes the dynamics of a protein in class of nuclear condensates. Also, the work expands the repertoire of nuclear tRNA synthetase roles to include regulation of RNA splicing, including of aaRS family member transcripts.
2023-04-14 | PXD015692 | Pride
Project description:Arginine is associated with inflammation, cancer, and amino acid signaling, in part through the mTORC1 pathway. In cell-based assays and in the mouse, we found that arginine regulates nuclear levels of arginyl-tRNA synthetase (ArgRS), and that arginine depletion and inflammation reduced nuclear ArgRS in vivo. In the nucleus, ArgRS interacted and co-localized with the spliceosomal Serine/Arginine Repetitive Matrix Protein 2 (SRRM2) that is crucial for the formation of nuclear speckle condensates. ArgRS mRNA silencing changed specific splice junction usages, and these inversely correlated with SRRM2-induced usage changes of the same junctions. The prominently affected genes encompassed components of the mTORC1 pathway and showed ArgRS, arginine, and SRRM2 are tied together as upstream regulators of nuclear condensate trafficking related to the physiological response to inflammatory injury. This study is the first to demonstrate a regulatory role for an aaRS in shaping nuclear condensate dynamics and RNA splicing.
2023-04-14 | PXD024091 | Pride
Project description:Arginine is involved in inflammation and amino acid signaling, in part through the mTORC1 pathway. In cell-based assays and in the mouse, we found that arginine regulates nuclear levels of arginyl-tRNA synthetase (ArgRS) and that nuclear ArgRS interacts and co-localizes with the Serine/Arginine Repetitive Matrix Protein 2 (SRRM2), a spliceosomal protein crucial for the formation of nuclear speckle condensates. Arginine depletion or ArgRS knock down, both of which decreased nuclear ArgRS levels, mobilized SRRM2 for trafficking from nuclear condensates and altered mRNA processing and splice junction usage while minimally affecting expression of other cellular RNAs. These splice junction changes included a subset that were inversely correlated with SRRM2 knock down induced changes and the affected genes encompassed components of the mTORC1 pathway. This inverse correlation suggests that the nuclear ArgRS-SRRM2 interaction regulates SRRM2 nuclear trafficking and alternative splicing in the physiological response to changed arginine levels resulting from inflammation.
2023-04-03 | GSE165513 | GEO
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:Impact of tRNA-Glu(UUC) and tRNA-Arg(CCG) on mRNA abundance
| PRJNA310009 | ENA
Project description:Impact of tRNA-Glu(UUC) and tRNA-Arg(CCG) on mRNA stability
| PRJNA310108 | ENA
Project description:Isoleucyl-tRNA synthetase 2, mitochondrial (IARS2) is a nuclear gene encoding a mitochondrial ARS. We used microarray analysis to identify the genes that are regulated by IARS2 in A549 cells.
2019-06-10 | GSE130007 | GEO
Project description:Stable expression of tRNA-Glu(UUC) and tRNA-Arg(CCG) followed by transcriptomic profiling to measure transcripts.
2016-06-07 | GSE77285 | GEO
Project description:Stable expression of tRNA-Glu(UUC) and tRNA-Arg(CCG) followed by whole-genome transcript stability measurements using a-amanitin mediated inhibition of RNA Pol II.
2016-06-07 | GSE77349 | GEO