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Accumulating evidence has confirmed the links between transfer RNA (tRNA) modifications and tumor progression. The present study is the first to explore the role of tRNA methyltransferase 5 (TRMT5), which catalyzes the m1G37 modification of mitochondrial tRNAs in hepatocellular carcinoma (HCC) progression. Here, based on bioinformatics and clinical analyses, we identified that TRMT5 expression was upregulated in HCC, which correlated with poor prognosis. Silencing TRMT5 attenuated HCC proliferation and metastasis both in vivo and in vitro, which may be partially explained by declined extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Mechanistically, we discovered that knockdown of TRMT5 inactivated the hypoxia-inducible factor-1 (HIF-1) signaling pathway by preventing HIF-1α stability through the enhancement of cellular oxygen content. Moreover, our data indicated that inhibition of TRMT5 sensitized HCC to doxorubicin by adjusting HIF-1α. In conclusion, our study revealed that targeting TRMT5 could inhibit HCC progression and increase the susceptibility of tumor cells to chemotherapy drugs. Thus, TRMT5 might be a carcinogenesis candidate gene that could serve as a potential target for HCC therapy.
Subject(s)
Humans , Carcinoma, Hepatocellular/pathology , Cell Hypoxia , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Liver Neoplasms/pathology , Signal Transduction/genetics , tRNA Methyltransferases/metabolismABSTRACT
Cancer is the second-leading cause of death worldwide. Cancer mortality is largely caused by the absence of recognizable early signs and a poor prognosis. Therefore, developing efficient diagnostic and prognostic biomarkers is crucial to reducing the incidence of cancer and improving its prognostic accuracy. tRNA-derived fragments are a new class of non-coding RNAs with important regulatory roles in cancer biology. In this paper, the research progress of tRNA-derived fragments as biomarkers in tumorigenesis, development, and prognosis was reviewed to provide a theoretical basis for cancer diagnosis and prognostic assessment.
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tRNA-derived small RNAs (tsRNAs) are novel non-coding RNAs that are involved in the occurrence and progression of diverse diseases. However, their exact presence and function in hepatocellular carcinoma (HCC) remain unclear. Here, differentially expressed tsRNAs in HCC were profiled. A novel tsRNA, tRNAGln-TTG derived 5'-tiRNA-Gln, is significantly downregulated, and its expression level is correlated with progression in patients. In HCC cells, 5'-tiRNA-Gln overexpression impaired the proliferation, migration, and invasion in vitro and in vivo, while 5'-tiRNA-Gln knockdown yielded opposite results. 5'-tiRNA-Gln exerted its function by binding eukaryotic initiation factor 4A-I (EIF4A1), which unwinds complex RNA secondary structures during translation initiation, causing the partial inhibition of translation. The suppressed downregulated proteins include ARAF, MEK1/2 and STAT3, causing the impaired signaling pathway related to HCC progression. Furthermore, based on the construction of a mutant 5'-tiRNA-Gln, the sequence of forming intramolecular G-quadruplex structure is crucial for 5'-tiRNA-Gln to strongly bind EIF4A1 and repress translation. Clinically, 5'-tiRNA-Gln expression level is negatively correlated with ARAF, MEK1/2, and STAT3 in HCC tissues. Collectively, these findings reveal that 5'-tiRJNA-Gln interacts with EIF4A1 to reduce related mRNA binding through the intramolecular G-quadruplex structure, and this process partially inhibits translation and HCC progression.
Subject(s)
Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Eukaryotic Initiation Factor-4A/genetics , Cell Line , RNA, Transfer/metabolism , RNA , Cell ProliferationABSTRACT
Las nuevas metodologías de secuenciación masiva han permitido caracterizar e identificar variantes genéticas asociadas a diferentes patologías. En este trabajo se presenta el caso de una paciente con una mutación del gen RARS2 que codifica la enzima arginino-ARNt ligasa para la codificación de proteínas. Esta alteración genética se manifiesta en hipoplasia pontocerebelosa tipo 6, con una prevalencia de <1/1 000 0000, caracterizada por un cerebelo y un puente de menor tamaño asociados a un retraso grave en el neurodesarrollo. El análisis de caso permite un mejor conocimiento de enfermedades de origen genético, específicamente, de aquellas con patrones de herencia autosómicos recesivos de padres no consanguíneos. Su estudio sobre todo en lo relacionado con el ámbito familiar y socioeconómico, y su base genética, ayuda a una mejor calidad de vida de los pacientes y su familia.
The latest method of next-generation sequencing has allowed the characterization and identification of genetic variants associated to diverse pathologies. In this article, we present the case of female patient with a mutation of the RARS2 gene that encodes the enzyme for arginyl tRNA synthetase for coding of proteins. This genetic alteration manifests in pontocerebellar hypoplasia type 6, with a prevalence of <1/1,000,0000, characterized by a cerebellum and pons that are smaller in size and are associated with severe neurodevelopmental delay. The analysis of the case of this patient provides better knowledge of diseases of genetic origin; specifically, regarding genetic diseases of autosomal recessive patterns of inheritance from non-consanguineous parents. The impact of these studies; specially within the family, social, economic and genetic aspects helps provide a better quality of life for these patients and their family.
Subject(s)
Humans , Female , Child, Preschool , Arginine-tRNA Ligase/genetics , Quality of Life , Magnetic Resonance Imaging , Sequence Analysis , Colombia , MutationABSTRACT
Objective:To investigate the effects of mitochondrial arginyl-tRNA synthase (RARS2) on cell proliferation, invasion, migration and chemotherapy resistance of pancreatic cancer.Methods:Human pancreatic cancer cell lines AsPC-1 and PANC-1 were divided into negative control group, RARS2 interference group-1, RARS2 interference group-2, RARS2 overexpression control group and RARS2 overexpression group. Cell proliferation and sensitivity to gemcitabine were detected by CCK-8 assay, and cell invasion and migration were detected by Transwell assay. Western blot was used to detect the expression of RARS2 under different concentrations and different times of gemcitabine treatment. Western blot and PCR were used to detect the expression of RARS2 in gemcitabine-resistant AsPC cell.Results:Inhibition of RARS2 expression in AsPC-1 and PANC-1 cells significantly inhibited cell proliferation and enhanced sensitivity of gemcitabine to chemotherapy. Overexpression of RARS2 enhanced cell proliferation and decreased sensitivity to gemcitabine. In AsPC-1 cells, the number of migrated cells (100×) in negative control group, RARS2 interference group-1, RARS2 interference group-2, RARS2 overexpression control group and RARS2 overexpression group were (586.7±37.4) cells/field, (195.7±18.6) cells/field, (237.0±17.1) cells/field, (157.7±19.1) cells/field, (456.0±23.1) cells/field, the number of invasive cells were (87.7±13.2) cells/field, (24.7±6.5) cells/field, (31.7±6.1) cells/field, (29.3±4.5) cells/field, (94.3±9.3) cells/field, respectively. The migration and invasion ability of cells were decreased after the expression of RARS2 was decreased, and the migration and invasion ability of cells were enhanced after the expression of RARS2 was increased. PCR and Western blot assay showed that RARS2 expression in the gemcitabine-resistant AsPC-1 was higher than that in the common cell line. In AsPC-1 cells, the expression of RARS2 increased with increasing gemcitabine concentration and treatment time.Conclusion:RARS2 promotes cell proliferation, invasion, migration and chemoresistance of pancreatic cancer, and expression of RARS2 is positively correlated with gemcitabine concentration and treatment time.
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Generation of mutants with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) is commonly carried out in fish species by co-injecting a mixture of Cas9 messenger RNA (mRNA) or protein and transcribed guide RNA (gRNA). However, the appropriate expression system to produce functional gRNAs in fish embryos and cells is rarely present. In this study, we employed a poly-transfer RNA (tRNA)-gRNA (PTG) system driven by cytomegalovirus (CMV) promoter to target the medaka (Oryzias latipes) endogenous gene tyrosinase(tyr) or paired box 6.1 (pax6.1) and illustrated its function in a medaka cell line and embryos. The PTG system was combined with the CRISPR/Cas9 system under high levels of promoter to successfully induce gene editing in medaka. This is a valuable step forward in potential application of the CRISPR/Cas9 system in medaka and other teleosts.
Subject(s)
Animals , CRISPR-Cas Systems , Cell Line , Gene Editing , Oryzias/genetics , /genetics , RNA, Transfer/geneticsABSTRACT
Objective:To analyze the expression of the recombinant human phenylalanine-tRNA ligase beta subunit(FARSB)gene in hepatocellular carcinoma(HCC)and explore its association with clinicopathologic characteristics and prognosis.Methods:Data sets of hepatocellular carcinoma and paracancerous tissues were downloaded from the Cancer Genome Atlas(TCGA), and the data were analyzed using the R and Perl programming languages.Cox regression and the Kaplan-Meier method were used to analyze the relationship between clinicopathological characteristics and overall survival.Gene set enrichment analysis(GSEA)was used to predict the signal pathways involved in the regulation of FARSB.qPCR and Western blot were used to verify the expression level of FARSB in hepatocellular carcinoma and adjacent tissues.Results:FARSB was highly expressed in HCC and the prognosis of HCC patients with high FARSB expression was poor.The clinical stage, T stage, M stage and FARSB were significantly correlated with overall survival, while only high FARSB expression was an independent prognostic factor in HCC patients.Conclusions:High expression of FARSB indicates a poor prognosis in HCC patients and FARSB can be used as a marker for poor prognosis in HCC.
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Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes(MELAS) is one of the most common inherited mitochondrial diseases. This paper reports a rare mutation associated with MELAS syndrome, the m. 3252 A>G mutation in the MT-TL1 gene encoding the mitochondrial tRNALeu(UUR). The 6-year-old girl suffered from recurrent convulsion and lactic acidemia. The mtDNA sequencing detected a variant m. 3252A>G(MT-TL1 gene) in the proband and her maternal relatives. The heteroplasmic levels in peripheral blood and urine sediment were 66.53% and 97.42%, respectively, which were obviously higher than those of her maternal relatives. Together with 3 previously reported cases, the variant m. 3252A>G could be classified pathogenic. All the reported pathogenic variants in MT-TL1 gene were reviewed to explore the genotype-phenotype correlations of pathogenic variants in MT-TL1 gene.
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SUMMARY OBJECTIVE: In this study, we aimed at investigating the role of isoleucyl-tRNA synthetase in the growth, migration, and angiogenesis of human umbilical vein endothelial cells and the underlying molecular mechanism. METHODS: To assess the role of isoleucyl-tRNA synthetase, we silenced isoleucyl-tRNA synthetase in human umbilical vein endothelial cells using lentiviral 2 specific short hairpin RNAs (short hairpin RNAs 1 and 2) and examined silencing efficiency using real time quantitative polymerase chain reaction and western blot analyses. Short hairpin RNAs 1-isoleucyl-tRNA synthetase had greater knockdown efficiency, it was used in the entire downstream analysis. Short hairpin RNAs 1- isoleucyl-tRNA synthetase silencing effects on cell proliferation, cell colony generation, cell migration, as well as angiogenesis were assessed using cell counting kit-8, colony development, cell migration, and angiogenesis tube formation assays, respectively. RESULTS: Compared to the control group, anti-isoleucyl-tRNA synthetase short hairpin RNAs significantly silenced isoleucyl-tRNA synthetase expression in human umbilical vein endothelial cells, and suppressed their proliferation, migration, and angiogenic capacity. To characterize the underlying mechanism, western blot analyses showed that isoleucyl-tRNA synthetase knockdown suppressed phosphorylation of extracellular-regulated kinase ½ and protein-serine- threonine kinase, as well as expression of vascular endothelial growth factor, GSK-3β, and β-catenin. CONCLUSIONS: We have shown, for the first time, the critical role of isoleucyl-tRNA synthetase in human umbilical vein endothelial cells. Our data show that isoleucyl-tRNA synthetase knockdown suppresses human umbilical vein endothelial cell proliferation, migration, and angiogenesis. We have also shown that isoleucyl-tRNA synthetase knockdown suppresses phosphorylation of extracellular-regulated kinase ½ and protein-serine- threonine kinase, as well as expression of vascular endothelial growth factor, GSK-3β, and β-catenin. Together, these data highlight isoleucyl-tRNA synthetase as a potential antitumor anti-angiogenic target.
Subject(s)
Humans , Vascular Endothelial Growth Factor A , Cells, Cultured , Cell Proliferation , Human Umbilical Vein Endothelial Cells , Glycogen Synthase Kinase 3 betaABSTRACT
BACKGROUND: Cross talk of tumorimmune cells at the gene expression level has been an area of intense research. However, it is largely unknown at the alternative splicing level which has been found to play important roles in the tumorimmune microenvironment. RESULTS: Here, we re-exploited one transcriptomic dataset to gain insight into tumorimmune interactions from the point of AS level. Our results showed that the AS profiles of triple-negative breast cancer cells co-cultured with activated T cells were significantly changed but not Estrogen receptor positive cells. We further suggested that the alteration in AS profiles in triple-negative breast cancer cells was largely caused by activated T cells rather than paracrine factors from activated T cells. Biological pathway analyses showed that translation initiation and tRNA aminoacylation pathways were most disturbed with T cell treatment. We also established an approach largely based on the AS factorAS events associations and identified LSM7, an alternative splicing factor, may be responsible for the major altered events. CONCLUSIONS: Our study reveals the notable differences of response to T cells among breast cancer types which may facilitate the development or improvement of tumor immunotherapy.
Subject(s)
T-Lymphocytes , Triple Negative Breast Neoplasms , Peptide Chain Initiation, Translational , Gene Expression , Alternative Splicing , Cell Culture Techniques , Receptor Cross-Talk , Transfer RNA Aminoacylation , Transcriptome , ImmunotherapyABSTRACT
Acetic acid is a common inhibitor present in lignocellulosic hydrolysate. Development of acetic acid tolerant strains may improve the production of biofuels and bio-based chemicals using lignocellulosic biomass as raw materials. Current studies on stress tolerance of yeast Saccharomyces cerevisiae have mainly focused on transcription control, but the role of transfer RNA (tRNA) was rarely investigated. We found that some tRNA genes showed elevated transcription levels in a stress tolerant yeast strain. In this study, we further investigated the effects of overexpressing an arginine transfer RNA gene tR(ACG)D and a leucine transfer RNA gene tL(CAA)K on cell growth and ethanol production of S. cerevisiae BY4741 under acetic acid stress. The tL(CAA)K overexpression strain showed a better growth and a 29.41% higher ethanol productivity than that of the control strain. However, overexpression of tR(ACG)D showed negative influence on cell growth and ethanol production. Further studies revealed that the transcriptional levels of HAA1, MSN2, and MSN4, which encode transcription regulators related to stress tolerance, were up-regulated in tL(CAA)K overexpressed strain. This study provides an alternative strategy to develop robust yeast strains for cellulosic biorefinery, and also provides a basis for investigating how yeast stress tolerance is regulated by tRNA genes.
Subject(s)
Acetic Acid , DNA-Binding Proteins/metabolism , Fermentation , Leucine , RNA, Transfer/genetics , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Transcription FactorsABSTRACT
RNA N6-methyladenosine (m6A) modification is an important gene expression regulation mechanism of eukaryotes. The m6A modification mainly mediates the methylation of adenosine N6. It is a reversible epigenetic modification that not only occurs in messenger RNA (mRNA), but also occurs in non-coding RNA (ncRNA). In addition, RNA m6A modification participates in many physiological and pathological processes, and also plays an important role in the occurrence and development of tumors. This article reviews the role of RNA m6A modification in malignant tumors of the digestive system.
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Objective:To investigate the clinical features, imaging features and gene mutation of a paitent with alanyl-transfer ribonucleic acid synthetase 2 (AARS2) gene mutation- related leukodystrophy and further improve the understanding of this rare disease.Methods:Clinical data of a patient with leukodystrophy associated with AARS2 gene mutation diagnosed in October 2020 at Xiamen Hospital of Beijing University of Chinese Medicine and Huashan Hospital of Fudan University were collected.Results:The male patient, 25 years old, was admitted with the clinical manifestations, including chronic onset dyskinesia, ataxia, nystagmus and psoriasis. Head magnetic resonance imaging (MRI) showed bilateral white matter lesions and cerebellar atrophy. Spine MRI showed vertebral body incomplete fusion. Gene detection showed heterozygous compound AARS2 gene mutation [c.985C>T chr6:44275041(p.R329C) and c.452T>C chr6:44279256(p.M151T)].Conclusions:AARS2 gene mutation-related leukodystrophy is a rare mitochondrial disease in clinical practice. The patient presented with progressive motor deficits in the lower limbs, ataxia, relatively retained cognitive function. MRI revealed abnormal symmetry of corpus callosum and bilateral paraventricular white matter. Heterozygous compound AARS2 gene mutations [c.985C>T chr6:44275041 (p.R329C) and c.452T>C chr6:44279256 (p.M151T)] are one of the pathogenic factors leading to hereditary leukodystrophy.
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Leucyl-tRNA synthetases (LRS) catalyze the linkage of leucine with tRNALeu. A large insertion CP1 domain(Connective Polypeptide 1) in LRS is responsible for post-transfer editing of mis-charged aminoacyl-tRNAs.Here, we characterized the CP1 domain of Leishmania donovani, a protozoan parasite, and its role in editingactivity and interaction with broad spectrum anti-fungal, AN2690. The deletion mutant of LRS, devoid of CP1domain (LRS-CP1D) was constructed, followed by determination of its role in editing and aminoacylation.Binding of AN2690 and different amino acids with CP1 deletion mutant and full length LRS was evaluatedusing isothermal titration calorimetry (ITC) and molecular dynamics simulations. The recombinant LRS-CP1Dprotein did not catalyze the aminoacylation and the editing reaction when compared to full-length LRS. Thus,indicating that CP1 domain was imperative for both aminoacylation and editing activities of LRS. Bindingstudies with different amino acids indicated selectivity of isoleucine by CP1 domain over other amino acids.These studies also indicated high affinity of AN2690 with the editing domain. Molecular docking studiesindicated that AN2690-CP1 domain complex was stabilized by hydrogen bonding and hydrophobic interactions resulting in high binding affinity between the two. Our data suggests CP1 is crucial for the function of L.donovani LRS.
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PURPOSE: Identification of lymph node (LN) metastasis in non-small cell lung cancer (NSCLC) is critical for disease staging and selection of therapeutic modalities. Sometimes it is not possible to obtain LN core tissue by endobronchial ultrasound-guided transbronchial needle aspirate (EBUS-TBNA), resulting in low diagnostic yield. MATERIALS AND METHODS: In this study, 138 specimens were collected from 108 patients who underwent EBUS-TBNA under the suspicion of LN metastasis of NSCLC. Diagnostic yields of anti-CD45 and anti-methionyl-tRNA synthetase (MRS), immunofluorescent (IF) staining on cytology specimens were compared with those of conventional cytology and positron emission tomography-computed tomography (PET-CT). RESULTS: MRS was strongly expressed in NSCLC cells metastasized to LNs, but weakly expressed in cells at the periphery of the LN germinal center. The majority of cells were CD20 positive, although a few cells were either CD3 or CD14 positive, indicating that CD45 staining is required for discrimination of non-malignant LN constituent cells from NSCLC cells. When the diagnostic efficacy of MRS/CD45 IF staining was evaluated using 138 LN cellular aspirates from 108 patients through EBUS-TBNA, the sensitivity was 76.7% and specificity was 90.8%, whereas those of conventional cytology test were 71.8% and 100.0%, respectively. Combining the results of conventional cytology testing and those of PET-CT showed a sensitivity and specificity of 71.6% and 100%, and the addition of MRS/CD45 dual IF data to this combination increased sensitivity and specificity to 85.1% and 97.8%, respectively. CONCLUSION: MRS/CD45 dual IF staining showed good diagnostic performance and may be a good tool complementing conventional cytology test for determining LN metastasis of NSCLC.
Subject(s)
Humans , Amino Acyl-tRNA Synthetases , Carcinoma, Non-Small-Cell Lung , Complement System Proteins , Discrimination, Psychological , Electrons , Germinal Center , Ligases , Lymph Nodes , Methionine-tRNA Ligase , Needles , Neoplasm Metastasis , Sensitivity and SpecificityABSTRACT
Translocation ribonucleic acid (tRNA) is one of the important components in protein synthesis. In order to explore the effect of the changes of tRNAs corresponding to rare codons (rarity tRNAs) on the expression of exogenous genes, the co-expression system of rare tRNA gene and exogenous gene in Pichia pastoris was constructed. The expression of GFP in P. pastoris can be greatly reduced when a repressor region composed of four continuous proline rare codon CCG was added into the GFP gene. The expression amount of the repressed GFP could be increased about 4.9% when tRNAProCCG gene was cointegrated to the 3' of the repressed GFP gene through pPIC9K to the genome of P. pastoris GS115. Meanwhile, the expression amount of the repressed GFP increased about 12.5% by integrating the repressed GFP gene and tRNAProCCG gene to the genome of P. pastoris GS115 through pPIC9K and pFLDα, respectively. Using the same method, NFATc3T-GFP fusion gene and tRNAProCCG gene were co-expressed in P. pastoris GS115 resulting in 21.3% increased of the expression amount of NFATc3T-GFP fusion protein. In conclusion, tRNAProCCG gene has been confirmed to be a kind of rare tRNAs in P. pastoris GS115. Through co-expression of tRNAProCCG gene and heterologous genes which containing the continuous rare codon CCG, the expression of the repressed heterologous genes could be increased significantly. Furthermore, this co-expression system would contribute to screening and determining the other rare tRNAs.
Subject(s)
Codon , Pichia , Recombinant ProteinsABSTRACT
The tRNA-derived fragments (tRF and tiRNA) are a newly discovered type of non-coding RNA (ncRNA) that has been found to be stably expressed in peripheral blood. Studies have shown that tRF and tiRNA play important roles in human tumors by regulating multiple processes, including gene expression and silencing, cell proliferation and apoptosis, and protein translation. The tissue-speci-ficity, high abundance, and stability of tRF and tiRNA, along with their broad-spectrum functional roles, confer them significant advan-tages for use in the field of oncology research. There is increasing evidence that aberrantly expressed tRF and tiRNA may be potential biomarkers or therapeutic targets for tumor diagnosis and prognosis. This paper summarizes the source, structure, biological charac-teristics, and functions of different tRF and tiRNA subtypes and explores their potential relationship with tumors and their underlying mechanisms in order to provide a novel idea for the early diagnosis and targeted therapy of tumors.
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Objective To investigate the clinical,serological and imaging features of antisynthetase syndrome (ASS) patients with different positive anti-aminoacyl-tRNA synthase (ARS) antibodies.Methods The demographic characteristics,major clinical data,serological parameters,high resolution CT (HRCT) imaging features and pulmonary function characteristics in 60 cases of ASS [including 42 cases with positive anti-histidine tRNA synthetase (Jo-1) antibody,and 7 cases with positive anti-threonyl tRNA synthetase (PL-7) antibody,5 cases with positive anti-alanyl tRNA synthetase (PL-12) antibody,3 cases with positive anti-glycyl tRNA synthetase (E J) antibody and 3 cases with positive anti-leucyl tRNA synthetase (OJ) antibody] were collected.The differences in ASS patients with different positive ARS antibodies were analyzed by the x2 test and Fisher exact test.Results ① The ASS with different positive ARS antibodies was common in patients with DM/PM,[60％ (36/60),28％ (17/60)],and also appeared in patients with other connective tissue diseases,such as RA(5％,3/60),SS(3％,2/60),SLE(2％,1/60),etc.With ASS diagnosed,ILD complicated with myositis was the most common clinical features (63％,38/60).Typical clinical triad syndrome (myositis,ILD and arthritis) in 52％(31/60) patients,and myositis complicated with ILD,and mechanics hands accounted for 38％ (23/60) respectively.Some patients were complicated with isolated arthritis (25％,15/60),myositis (23％,14/60) and ILD (13％,8/60).The typical triad syndrome (myositis,ILD and arthritis) only accounted for 5％(3/60).The incidence of Jo-1,EJ and OJ antibodies [71％(30/42),100％(3/3),100％(3/3)] was significantly higher than that of PL-12 antibody (20％,1/5).There was a statistically significant difference (x2=5.263,P＜0.05;x2=4.8,P＜ 0.05;x2=4.8,P＜0.05).② The positive rate of ANA was 98％(59/60).Furthermore,the fluorescence staining model of anti-OJ antibody ANA was spotted,and the other subtypes were cytosolic.The positive rate of anti-SSA-52 antibody was 45％(27/60),and there was no statistical difference between the subtypes (P＞0.05).③ The ILD incidence of different positive antibodies had no significant difference in 82％ (49/60) ASS patients with ILD.The lung function in patients with ASS-ILD showed restrictive ventilation and diffused dysfunction.Grid shadow (76％,37/49) and grind glass (35％,17/49) were the most common signs of HRCT.Nonspecific interstitial pneumonia (NSIP) (78％,38/49) was the most common subtype of ILD.The incidence of traction bronchiectasis in ASS patients with PL-12 antibody (75％,3/4) was higher than that in ASS patients with Jo-1 antibody (22％,8/36).The incidence of pleural effusion in ASS patients with OJ antibody (100％,2/2) was significantly higher than that in ASS patients with Jo-1 antibody (17％,6/36).The incidence of pericardial effusion in ASS patients with PL-7 antibody (75％,3/4) was significantly higher than that in ASS patients with Jo-1 antibody (19.4％,7/36).All the differences were statistically significant (x2=5.26,P＜0.05).The ASS-ILD lung function indicated restrictive ventilatory function and diffusion dysfunction.④ There was no significant difference in clinical data,serological indicators,ILD imaging findings,interstitial lung types and lung function between Jo-1 antibody and non-Jo-1 antibody ASS patients (P＞0.05).Conclusion The ASS with different positive ARS antibodies is very common in patients with DM/PM,and is also observed in patients with other connective tissue diseases.ILD and myositis are the most common clinical features of ASS,followed by the typical triad syndrome (myositis,ILD and arthritis).Myositis is commonly observed in ASS patients with Jo-1,EJ and OJ antibodies,while is rarely observed in ASS patients with PL-12 antibody.The diagnosis of ASS should be alert to the onset of isolated arthritis or ILD.Anti-SSA-52 antibody may be related to ASS.NSIP is the most common HRCT pattern in ASS-ILD patients.There are some differences in signs among various subtypes,indicating that the difference of fibrosis in the lung and inflammatory reactions in the body being correlated with the ASS specificities.
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The presence of tRNA array, a region with high tRNA gene number and density, has been demonstrated in Mycobacterium genus. However, a recent phylogenomic study revealed the existence of five distinct monophyletic groups (genera) within this genus. Considering this new scenario, and based on in-silico analyses, we have identified and characterised the abundance and diversity of tRNA array units within Mycobacterium, Mycolicibacterium gen. nov., Mycolicibacillus gen. nov., and Mycobacteroides gen. nov. The occurrence and prevalence of tRNA arrays among the genera belonging to Actinobacteria indicate their possible role in the organismal fitness.
Subject(s)
Bacterial Typing Techniques , Mycobacterium/genetics , Phylogeny , RNA, Transfer/genetics , Mycobacterium/classificationABSTRACT
BACKGROUND Shared traits between prokaryotes and eukaryotes are helpful in the understanding of the tree of life evolution. In bacteria and eukaryotes, it has been shown a particular organisation of tRNA genes as clusters, but this trait has not been explored in the archaea domain. OBJECTIVE Explore the occurrence of tRNA gene clusters in archaea. METHODS In-silico analyses of complete and draft archaeal genomes based on tRNA gene isotype and synteny, tRNA gene cluster content and mobilome elements. FINDINGS We demonstrated the prevalence of tRNA gene clusters in archaea. tRNA gene clusters, composed of archaeal-type tRNAs, were identified in two Archaea class, Halobacteria and Methanobacteria from Euryarchaeota supergroup. Genomic analyses also revealed evidence of the association between tRNA gene clusters to mobile genetic elements and intra-domain horizontal gene transfer. MAIN CONCLUSIONS tRNA gene cluster occurs in the three domains of life, suggesting a role of this type of tRNA gene organisation in the biology of the living organisms.