Brucella tRNA-derived fragment tRF-Leu-CAG reprograms macrophage polarization for intracellular survival via up-regulation of IL13RA1 expression
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ABSTRACT:
PROVIDER: PRJNA1214379 | ENA |
REPOSITORIES: ENA
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Project description:Outer membrane vehicles (OMVs) are secreted from gram-negative bacterium to enable bacterial survival and regulate microbial interactions within bacterial communities. The components of OMVs comprise RNA, but the generation as well as the function of OMVs RNA needs to be elucidated. Here, we report that a small non-coding RNA fragment tRF-Leu-CAG, detected in Brucella OMVs, regulates interleukin 13 receptor subunit alpha 1 (IL13RA1) to activate the phosphorylation of Signal Transducer and activator of Transcription 6 (STAT6) via the JAK-STAT6 pathway to reprogram macrophage M2 polarization. We identified the presence of tRF-Leu-CAG in Brucella OMVs by sRNA sequencing and tRF sequencing from bacterial lysate. tRF-Leu-CAG interacts with argonaute 2 (AGO2) protein to exert its function. Meanwhile, the interleukin 13 receptor subunit alpha 1 (IL13RA1) was proved to be the target genes of tRF-Leu-CAG. Overexpression of phosphorylated STAT6 by western blot further substantiated that tRF-Leu-CAG promotes macrophage M2 polarization via the JAK-STAT6 pathway. Finally, tRF-Leu-CAG and small interfering IL13RA1 facilitates the survival of Brucella in macrophage. Thus, our results highlight the function of tRF-Leu-CAG in Brucella OMVs by reprogramming macrophage M2 polarization to improve the survival of extracellular Brucella. The study unravels a new mechanism of intracellular parasitism and immune escape in Brucella, providing strategy for the mechanisms of other intracellular parasitic bacteria.
2025-01-27 | GSE287747 | GEO
Project description:In this study, we discovered cytosolic and mitochondrial fragments resulting from tRNA and mt-tRNA cleavage, which may act as new regulators of cellular and metabolic functions. We selected the mt-tRF-LeuTAA fragment for further investigation, as its level is altered in the islets diabetes-susceptible animal models, while being abundant in ß-cells. mt-tRF-LeuTAA fragment is derived from the cleavage of tRNA-LeuTAA encoded by the mitochondrial genome. We demonstrated that mt-tRF-LeuTAA acts as a key regulator of mitochondrial OXPHOS functions, mitochondrial membrane potential, the insulin secretory capacity of ß-cells, and the insulin sensitivity of myotube muscle cells. To gain a comprehensive understanding, we conducted transcriptomic and proteomic analyses on rat islets with silenced mt-tRF-LeuTAA for 72 hours. We transfected rat islet cells with an antisense oligonucleotides (antisense oligonucleotides to reduce mt-tRF-LeuTAA levels versus control oligos). These oligos specifically decreased the levels of the fragment (anti-tRF-LeuTAA) by more than 95% without affecting the host full-length tRNA mt-tRNA-LeuTAA. Inhibiting mt-tRF-LeuTAA led to significant differential expression of 4843 mRNA transcripts, cut-off adjusted P ≤ 0.05. To further investigate the cellular rearrangement associated with the inhibition of mt-tRF-LeuTAA, we conducted enrichment analysis using Gene Ontology Molecular Function terms on RNA-sequencing. At the transcriptomic level, we observed enrichment of pathways related to ion transport and various enzymatic activities, including mitochondrial oxidoreductase activity, when the mitochondrial fragment was repressed in rat islets.
2024-05-14 | GSE240395 | GEO
Project description:In the yeast genera Saccharomycopsis and Ascoidea, nuclear genes use a non-standard genetic code in which CUG codons are translated as serine instead of leucine, due to the presence of a tRNA-Ser with the unusual anticodon CAG. However, some species in this ‘CUG-Ser2’ clade also contain an ancestral tRNA-Leu gene with the same anticodon. One of these species, Ascoidea asiatica, has been shown to have a stochastic proteome in which proteins contain approximately 50% Ser and 50% Leu at CUG codon sites, whereas previously examined Saccharomycopsis species translate CUG only as Ser. Here, we investigated the presence, conservation, and possible functionality of the tRNA-Leu(CAG) gene in the genus Saccharomycopsis. We analyzed the genomes of 33 strains, including almost all known species of Saccharomycopsis, and found that most of them contain both tRNA-Ser(CAG) and tRNA-Leu(CAG) genes. The tRNA-Leu(CAG) gene is evolving faster than tRNA-Ser(CAG) and it has been lost in two species, S. microspora and S. synnaedendra. We deleted the single tRNA-Leu(CAG) gene in S. capsularis and found that it is not essential. Bioinformatic analysis suggested that some CUG codon sites in Saccharomycopsis species may be translated as Leu, specifically in genes with functions in meiosis or sporulation, but mass spectrometry of sporulating S. capsularis and S. fermentans cultures showed only CUG-Ser translation. Cloverleaf structures of tRNA-Leu(CAG) from all Saccharomycopsis species contain mutations that are likely to make them non-functional in translation, but the evolutionary conservation of the gene leads us to propose that it has been retained for an unknown non-translational role.
2024-10-17 | PXD044729 | Pride
Project description:In the yeast genera Saccharomycopsis and Ascoidea, nuclear genes use a non-standard genetic code in which CUG codons are translated as serine instead of leucine, due to the presence of a tRNA-Ser with the unusual anticodon CAG. However, some species in this ‘CUG-Ser2’ clade also contain an ancestral tRNA-Leu gene with the same anticodon. One of these species, Ascoidea asiatica, has been shown to have a stochastic proteome in which proteins contain approximately 50% Ser and 50% Leu at CUG codon sites, whereas previously examined Saccharomycopsis species translate CUG only as Ser. Here, we investigated the presence, conservation, and possible functionality of the tRNA-Leu(CAG) gene in the genus Saccharomycopsis. We analyzed the genomes of 33 strains, including almost all known species of Saccharomycopsis, and found that most of them contain both tRNA-Ser(CAG) and tRNA-Leu(CAG) genes. The tRNA-Leu(CAG) gene is evolving faster than tRNA-Ser(CAG) and it has been lost in two species, S. microspora and S. synnaedendra. We deleted the single tRNA-Leu(CAG) gene in S. capsularis and found that it is not essential. Bioinformatic analysis suggested that some CUG codon sites in Saccharomycopsis species may be translated as Leu, specifically in genes with functions in meiosis or sporulation, but mass spectrometry of sporulating S. capsularis and S. fermentans cultures showed only CUG-Ser translation. Cloverleaf structures of tRNA-Leu(CAG) from all Saccharomycopsis species contain mutations that are likely to make them non-functional in translation, but the evolutionary conservation of the gene leads us to propose that it has been retained for an unknown non-translational role.
2024-10-17 | PXD044731 | Pride
Project description:In the yeast genera Saccharomycopsis and Ascoidea, nuclear genes use a non-standard genetic code in which CUG codons are translated as serine instead of leucine, due to the presence of a tRNA-Ser with the unusual anticodon CAG. However, some species in this ‘CUG-Ser2’ clade also contain an ancestral tRNA-Leu gene with the same anticodon. One of these species, Ascoidea asiatica, has been shown to have a stochastic proteome in which proteins contain approximately 50% Ser and 50% Leu at CUG codon sites, whereas previously examined Saccharomycopsis species translate CUG only as Ser. Here, we investigated the presence, conservation, and possible functionality of the tRNA-Leu(CAG) gene in the genus Saccharomycopsis. We analyzed the genomes of 33 strains, including almost all known species of Saccharomycopsis, and found that most of them contain both tRNA-Ser(CAG) and tRNA-Leu(CAG) genes. The tRNA-Leu(CAG) gene is evolving faster than tRNA-Ser(CAG) and it has been lost in two species, S. microspora and S. synnaedendra. We deleted the single tRNA-Leu(CAG) gene in S. capsularis and found that it is not essential. Bioinformatic analysis suggested that some CUG codon sites in Saccharomycopsis species may be translated as Leu, specifically in genes with functions in meiosis or sporulation, but mass spectrometry of sporulating S. capsularis and S. fermentans cultures showed only CUG-Ser translation. Cloverleaf structures of tRNA-Leu(CAG) from all Saccharomycopsis species contain mutations that are likely to make them non-functional in translation, but the evolutionary conservation of the gene leads us to propose that it has been retained for an unknown non-translational role.
2024-10-17 | PXD044772 | Pride
Project description:In the yeast genera Saccharomycopsis and Ascoidea, nuclear genes use a non-standard genetic code in which CUG codons are translated as serine instead of leucine, due to the presence of a tRNA-Ser with the unusual anticodon CAG. However, some species in this ‘CUG-Ser2’ clade also contain an ancestral tRNA-Leu gene with the same anticodon. One of these species, Ascoidea asiatica, has been shown to have a stochastic proteome in which proteins contain approximately 50% Ser and 50% Leu at CUG codon sites, whereas previously examined Saccharomycopsis species translate CUG only as Ser. Here, we investigated the presence, conservation, and possible functionality of the tRNA-Leu(CAG) gene in the genus Saccharomycopsis. We analyzed the genomes of 33 strains, including almost all known species of Saccharomycopsis, and found that most of them contain both tRNA-Ser(CAG) and tRNA-Leu(CAG) genes. The tRNA-Leu(CAG) gene is evolving faster than tRNA-Ser(CAG) and it has been lost in two species, S. microspora and S. synnaedendra. We deleted the single tRNA-Leu(CAG) gene in S. capsularis and found that it is not essential. Bioinformatic analysis suggested that some CUG codon sites in Saccharomycopsis species may be translated as Leu, specifically in genes with functions in meiosis or sporulation, but mass spectrometry of sporulating S. capsularis and S. fermentans cultures showed only CUG-Ser translation. Cloverleaf structures of tRNA-Leu(CAG) from all Saccharomycopsis species contain mutations that are likely to make them non-functional in translation, but the evolutionary conservation of the gene leads us to propose that it has been retained for an unknown non-translational role.
2024-10-17 | PXD044719 | Pride
Project description:In the yeast genera Saccharomycopsis and Ascoidea, nuclear genes use a non-standard genetic code in which CUG codons are translated as serine instead of leucine, due to the presence of a tRNA-Ser with the unusual anticodon CAG. However, some species in this ‘CUG-Ser2’ clade also contain an ancestral tRNA-Leu gene with the same anticodon. One of these species, Ascoidea asiatica, has been shown to have a stochastic proteome in which proteins contain approximately 50% Ser and 50% Leu at CUG codon sites, whereas previously examined Saccharomycopsis species translate CUG only as Ser. Here, we investigated the presence, conservation, and possible functionality of the tRNA-Leu(CAG) gene in the genus Saccharomycopsis. We analyzed the genomes of 33 strains, including almost all known species of Saccharomycopsis, and found that most of them contain both tRNA-Ser(CAG) and tRNA-Leu(CAG) genes. The tRNA-Leu(CAG) gene is evolving faster than tRNA-Ser(CAG) and it has been lost in two species, S. microspora and S. synnaedendra. We deleted the single tRNA-Leu(CAG) gene in S. capsularis and found that it is not essential. Bioinformatic analysis suggested that some CUG codon sites in Saccharomycopsis species may be translated as Leu, specifically in genes with functions in meiosis or sporulation, but mass spectrometry of sporulating S. capsularis and S. fermentans cultures showed only CUG-Ser translation. Cloverleaf structures of tRNA-Leu(CAG) from all Saccharomycopsis species contain mutations that are likely to make them non-functional in translation, but the evolutionary conservation of the gene leads us to propose that it has been retained for an unknown non-translational role.
2024-10-17 | PXD044788 | Pride
Project description:In the yeast genera Saccharomycopsis and Ascoidea, nuclear genes use a non-standard genetic code in which CUG codons are translated as serine instead of leucine, due to the presence of a tRNA-Ser with the unusual anticodon CAG. However, some species in this ‘CUG-Ser2’ clade also contain an ancestral tRNA-Leu gene with the same anticodon. One of these species, Ascoidea asiatica, has been shown to have a stochastic proteome in which proteins contain approximately 50% Ser and 50% Leu at CUG codon sites, whereas previously examined Saccharomycopsis species translate CUG only as Ser. Here, we investigated the presence, conservation, and possible functionality of the tRNA-Leu(CAG) gene in the genus Saccharomycopsis. We analyzed the genomes of 33 strains, including almost all known species of Saccharomycopsis, and found that most of them contain both tRNA-Ser(CAG) and tRNA-Leu(CAG) genes. The tRNA-Leu(CAG) gene is evolving faster than tRNA-Ser(CAG) and it has been lost in two species, S. microspora and S. synnaedendra. We deleted the single tRNA-Leu(CAG) gene in S. capsularis and found that it is not essential. Bioinformatic analysis suggested that some CUG codon sites in Saccharomycopsis species may be translated as Leu, specifically in genes with functions in meiosis or sporulation, but mass spectrometry of sporulating S. capsularis and S. fermentans cultures showed only CUG-Ser translation. Cloverleaf structures of tRNA-Leu(CAG) from all Saccharomycopsis species contain mutations that are likely to make them non-functional in translation, but the evolutionary conservation of the gene leads us to propose that it has been retained for an unknown non-translational role.
2024-10-17 | PXD044786 | Pride
Project description:In the yeast genera Saccharomycopsis and Ascoidea, nuclear genes use a non-standard genetic code in which CUG codons are translated as serine instead of leucine, due to the presence of a tRNA-Ser with the unusual anticodon CAG. However, some species in this ‘CUG-Ser2’ clade also contain an ancestral tRNA-Leu gene with the same anticodon. One of these species, Ascoidea asiatica, has been shown to have a stochastic proteome in which proteins contain approximately 50% Ser and 50% Leu at CUG codon sites, whereas previously examined Saccharomycopsis species translate CUG only as Ser. Here, we investigated the presence, conservation, and possible functionality of the tRNA-Leu(CAG) gene in the genus Saccharomycopsis. We analyzed the genomes of 33 strains, including almost all known species of Saccharomycopsis, and found that most of them contain both tRNA-Ser(CAG) and tRNA-Leu(CAG) genes. The tRNA-Leu(CAG) gene is evolving faster than tRNA-Ser(CAG) and it has been lost in two species, S. microspora and S. synnaedendra. We deleted the single tRNA-Leu(CAG) gene in S. capsularis and found that it is not essential. Bioinformatic analysis suggested that some CUG codon sites in Saccharomycopsis species may be translated as Leu, specifically in genes with functions in meiosis or sporulation, but mass spectrometry of sporulating S. capsularis and S. fermentans cultures showed only CUG-Ser translation. Cloverleaf structures of tRNA-Leu(CAG) from all Saccharomycopsis species contain mutations that are likely to make them non-functional in translation, but the evolutionary conservation of the gene leads us to propose that it has been retained for an unknown non-translational role.
2024-10-17 | PXD044742 | Pride
Project description:In the yeast genera Saccharomycopsis and Ascoidea, nuclear genes use a non-standard genetic code in which CUG codons are translated as serine instead of leucine, due to the presence of a tRNA-Ser with the unusual anticodon CAG. However, some species in this ‘CUG-Ser2’ clade also contain an ancestral tRNA-Leu gene with the same anticodon. One of these species, Ascoidea asiatica, has been shown to have a stochastic proteome in which proteins contain approximately 50% Ser and 50% Leu at CUG codon sites, whereas previously examined Saccharomycopsis species translate CUG only as Ser. Here, we investigated the presence, conservation, and possible functionality of the tRNA-Leu(CAG) gene in the genus Saccharomycopsis. We analyzed the genomes of 33 strains, including almost all known species of Saccharomycopsis, and found that most of them contain both tRNA-Ser(CAG) and tRNA-Leu(CAG) genes. The tRNA-Leu(CAG) gene is evolving faster than tRNA-Ser(CAG) and it has been lost in two species, S. microspora and S. synnaedendra. We deleted the single tRNA-Leu(CAG) gene in S. capsularis and found that it is not essential. Bioinformatic analysis suggested that some CUG codon sites in Saccharomycopsis species may be translated as Leu, specifically in genes with functions in meiosis or sporulation, but mass spectrometry of sporulating S. capsularis and S. fermentans cultures showed only CUG-Ser translation. Cloverleaf structures of tRNA-Leu(CAG) from all Saccharomycopsis species contain mutations that are likely to make them non-functional in translation, but the evolutionary conservation of the gene leads us to propose that it has been retained for an unknown non-translational role.
2024-10-17 | PXD044785 | Pride