Very little is known about splicing and its regulation in germ cells, particularly during meiosis. This paper describes the role of a male germ cell-specific protein, Tudor containing protein 6 (TDRD6), in assembly of the spliceosome in spermatocytes. We show that in spermatocytes, TDRD6 interacts with the key protein methyl transferase of the splicing pathway PRMT5. PRMT5 methylates arginines in substrate proteins. In a methylation dependent manner, TDRD6 also associates with spliceosomal core protein SmB in the absence of RNA, thus before an RNP-type spliceosome has been assembled. In Tdrd6-/- primary spermatocytes, PRMT5''s association with SmB and the arginine dimethylation of SmB are much reduced. Abrogation of arginine methylation impaired the assembly of spliceosomes and the presence of the spliceosomal RNA U5 is aberrantly increased. These deficiencies in spliceosome maturation correlated with decreased numbers of Cajal bodies and gems involved in later stages, i.e. nuclear snRNP maturation. To reveal functional consequences of these deficiencies, transcriptome analysis of primary spermatocytes showed high numbers of splicing defects such as aberrant usage of intron and exons as well as aberrant representation of splice junctions upon TDRD6 loss. This study reveals a novel function of TDRD6 in spliceosome maturation and mRNA splicing in spermatocytes. Overall design: Examination of splicing defects in isolated diplotene cells of 20dpp Tdrd6-/- vs. Tdrd6+/- testes pooled from at least 4 mice by deep sequencing in duplicate using Illumina® HiSeq 2500.
TDRD6 mediates early steps of spliceosome maturation in primary spermatocytes.
Specimen part, Subject
View SamplesDigital gene expression profiling was used to invesigate the differetiated genes between primary mouse hepatic stellate cells infected with AGGF1 adenovirus particles or negative control adenovirus pairticles. Overall design: Primary hepatic stellate cells isolated from mice were cultured in vitro, infected with AGGF1 adenovirus particles or negative control adenovirus particles, at day 8, total RNA were prepared and used for digital gene expression tag profiling.
Angiogenic factor with G patch and FHA domains 1 (Aggf1) regulates liver fibrosis by modulating TGF-β signaling.
Specimen part, Cell line, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Synovium-Derived MicroRNAs Regulate Bone Pathways in Rheumatoid Arthritis.
Specimen part, Time
View SamplesTo find regulated genes during peak inflammation of rheumatoid arthritis (RA), we have collected synovium from mouse Serum Transfer Arthtitis (STA) model at day 0 (Non Arthritic) and day 10 (Peak Inflammation).
Synovium-Derived MicroRNAs Regulate Bone Pathways in Rheumatoid Arthritis.
Specimen part, Time
View SamplesRibosome profiling of MDA-MB-231 cells treated with Silvestrol to monitor transcriptome wide, eIF4A-dependent changes in translation efficiency Overall design: Translation efficiency (TE) of mRNAs dervied from ribosome footprints was monitored in the presence or absence of 25 nM Silvestrol, an inhibitor of eukaryotic translation initiation factor 4A (eIF4A). Transcripts with reduced TE in the presence of Silvestrol were compare to transcripts with reduced TE in the presence of INK128, a catalytic mTOR inhbitor.
Transcriptome-wide characterization of the eIF4A signature highlights plasticity in translation regulation.
No sample metadata fields
View SamplesThe growth and fruit quality of grapevine are widely affected by abnormal climatic conditions such as water deficit. But how grapevine responds to drought stress is still largely unknown. Here we found that VaNAC26, a member of NAC transcription factor family, was up-regulated dramatically during cold, drought and salinity treatments in Vitis amurensis, a cold and drought-hardiness wild Vitis species. Ectopic overexpression of VaNAC26 enhanced the drought and salt tolerances in transgenic Arabidopsis. Higher activities of antioxidant enzymes and the lower concentration of H2O2 and O2- were found in VaNAC26-OE lines than in wild type plants under drought stress. These results indicate that the reactive oxygen species (ROS) scavenging was enhanced by VaNAC26 in transgenic lines. Microarray based transcriptome analysis reveals that genes related to jasmonic acid (JA) synthesis and signaling were up-regulated in VaNAC26-OE lines under both normal and drought conditions. VaNAC26 showed a specific binding ability on NACRS motif, which was broadly existent in the promoter regions of up-regulated genes in transgenic lines. Endogenous JA content was found increased obviously in VaNAC26-OE-2/3 lines. Our data suggests that VaNAC26 responds to abiotic stresses and may enhance the drought tolerance by transcriptional regulation of JA synthesis in Arabidopsis.
Expression of Vitis amurensis NAC26 in Arabidopsis enhances drought tolerance by modulating jasmonic acid synthesis.
Specimen part
View SamplesAbraxane, a nanoparticle (NP) formulation of paclitaxel (PTX), has been demonstrated to be more effective than Taxol, the small molecule formulation, for the treatment of breast cancer and non-small cell lung cancer (NSCLC). It was reported that Abraxane existed in plasma as particles with the size of ~10 nm. NPs get in and out of the cells by endocytosis and exocytosis, whereas small molecules by diffusion and efflux. It is intriguing to know whether the improved pharmaceutical performance is related to the “too-big-to-be-pumped-out” phenomenon. Here we established an Abraxane-resistant NSCLC cell line A549/Abr and compared its transcriptomes with that of the Abraxane-sensitive parental cell line by RNA-Seq technology. To our surprise, the most significantly up-regulated genes were ABC transporters, the common efflux pump for small molecules. We further found that the ABCB1 inhibitor Verapamil reversed the drug resistance and confirmed the important role of ABCB1 in Abraxane resistance. Overall design: mRNA profiles of A549 and A549/Abr cells were generated using Illumina Hiseq 2000 and compared.
Abraxane, the Nanoparticle Formulation of Paclitaxel Can Induce Drug Resistance by Up-Regulation of P-gp.
No sample metadata fields
View SamplesOculo-facio-cardio-dental syndrome (OFCD) is a rare genetic disorder characterized by teeth with extremely long roots (radiculomegaly), and craniofacial, eye and cardiac abnormalities. The mutation of the transcriptional co-repressor BCOR has been identified as being responsible for oculo-facio-cardio-dental (OFCD) syndrome.
BCOR regulates mesenchymal stem cell function by epigenetic mechanisms.
Specimen part
View SamplesCryptococcal osteomyelitis is an infrequent infection which is usually associated with disseminated cryptococcosis or underlying immunocompromised conditions. Here we described a rare case with isolated iliac cryptococcosis in an immunocompetent patient. Through histological, microbial, and molecular biological examinations, the pathogen was finally identified as C. neoformans VNI genotype, which likely originated from environmental bird droppings. The clinical isolate was hypomelanized but fully virulent in mouse infection model. The patient displayed lower CD4+-T lymphocyte ratio, reduced serum IFN-? and IL-12, and dysregulated transcriptional profile of blood leukocytes compare with healthy host. After surgical excision and 34 weeks' antifungal treatment, the patient got clinical cured. Our study suggested that cryptococcosis development was closely associated with the interaction of fungal agent and host immunity. Accurate diagnosis of bone cryptococcosis depends mainly on histological and fungal examinations. A combination of antifungal agent treatment regimen and surgery were quite effective for resolving bone cryptococcosis. Overall design: mRNA profiles of an Immunocompetent Patient and normal control''s blood were generated by deep sequencing, using Illumina HiSeq 2500
Isolated iliac cryptococcosis in an immunocompetent patient.
Sex, Specimen part, Subject
View SamplesExpression profiling of whole body (WB) FXR knockout (KO) mice (FXR WB KO), liver-specific FXR KO mice (AFXR Cre+) and enterocyte specific FXR KO mice (VFXR Cre+) on a C57BL/6J genetic background
Genome-wide binding and transcriptome analysis of human farnesoid X receptor in primary human hepatocytes.
Sex, Specimen part, Treatment
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