XRN2 is a conserved 5’-->3’ exoribonuclease that complexes with XTB-domain containing proteins. Thus, in Caenorhabditis elegans (C. elegans), the XTBD-protein PAXT-1 stabilizes XRN2 to retain its activity. XRN2 activity is also promoted by 3''(2''),5''-bisphosphate nucleotidase 1 (BPNT1) through its hydrolysis of 3’-phosphoadenosine-5''-bisphosphate (PAP), an endogenous XRN inhibitor. Here, we find through unbiased screening that loss of bpnt-1 function suppresses lethality caused by paxt-1 deletion. This unexpected finding is explained by XRN2 autoregulation, which occurs through repression of a cryptic promoter activity and destabilization of the xrn-2 transcript. Autoregulation appears to be triggered at different thresholds of XRN2 inactivation, such that more robust XRN2 perturbation, by elimination of both PAXT-1 and BPNT1, is less detrimental to worm viability than absence of PAXT-1 alone. Like more than 15% of C. elegans genes, xrn-2 occurs in an operon, and we identify additional operons under its control, consistent with a broader function of XRN2 in polycistronic gene regulation. Regulation occurs through intercistronic regions that link genes in an operon, but similar mechanisms may allow XRN2 to operate on monocistronic genes in organisms lacking operons. Overall design: Wild-type C. elegans worms were subjected to mock or xrn-2 RNAi from L1 to L4 stage at 20°C. Total RNA was extracted from the worms, and polyadenylated RNA was analyzed.
XRN2 Autoregulation and Control of Polycistronic Gene Expresssion in Caenorhabditis elegans.
Cell line, Subject
View SamplesThe seed coat of black (iRT) soybean with the dominant R allele begins to accumulate cyanic pigments at the transition stage of seed development (300 400 mg fresh seed weight), whereas the brown (irT) nearly-isogenic seed coat with the recessive r allele lacks cyanic pigments at all stages of seed development.
Combined analysis of transcriptome and metabolite data reveals extensive differences between black and brown nearly-isogenic soybean (Glycine max) seed coats enabling the identification of pigment isogenes.
Specimen part
View SamplesmicroRNAs (miRNAs) constitute a class of small non-coding RNAs (~22nt). They are thought to be generally stable with half-lives of many hours or even days. However, several miRNAs have been reported to decay rapidly in specific situations. In order to examine miRNA stability on a global scale, we quantify relative decay rates of miRNA in first larval stage C. elegans worms that are treated with a transcription inhibitor alpha-amanitin by deep sequencing. Several miRNAs including members of the miR-35 and miR-51 families exhibit accelerated decay. Moreover, biogenesis of miRNAs involves generation of a miRNA duplex intermediate consisting of the miRNA guide strand (miR) and the miRNA passenger strand (miR*). miR and miR* names were originally assigned based on the relative abundance of each strand, with the less abundant strand presumed to be inactive, and thus the miR*. However, subsequent research showed that at least individual miR*s can have biological activity. Our sequencing data reveal that miR*s, operationally defined on the basis of their relative abundance at time point t=1h, are substantially less stable than miRs. This would appear to support the notion that miR*s mainly constitute processing byproducts rather than a less abundant class of functional miRNAs. Overall design: Examination of microRNA decay rates in the first larval stage C. elegans worms.
Engineering of a conditional allele reveals multiple roles of XRN2 in Caenorhabditis elegans development and substrate specificity in microRNA turnover.
Specimen part, Cell line, Treatment, Subject
View SamplesThe purpose of this study is to obtain comprehensive gene expression profiles in breast cancer. Mammary gland cells were specifically isolated from 433 clinical tissue samples by laser capture microdissection (LCM). Total RNAs were extracted from LCM captured samples. We investigated gene expression profiles in 417 patients with breast cancer and 16 non-tumor tissues as a normal control using an Affymetrix GeneChip.
Epithelial-mesenchymal transition spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients.
Specimen part
View SamplesThe regulatory mechanisms that shapes the hepatic zonation is not well understood. In addition, the concept and significance of of hepatic zonation is well established in rodens, however, its relavence to human liver biology remain elusive. We conducted a comprehensive transcriptome analysis of each zonation within normal human liver vis Laser Capture Microdissection approach. Here, we report a poly A RNA sequencing data of the individual zone of liver tissue as well as the whole liver of the corresponding subjects. Overall design: The RNA samples were collected from each zone within hepatic lobule by a Laser Captured Microdissection approach. This study examined the gene expression profile in each zone of the normal human liver.
Dual modulation of human hepatic zonation via canonical and non-canonical Wnt pathways.
Sex, Subject
View SamplesThis experiment is to identify genes that are regulated by pRb in AC61 cells. AC61 cells were derived from a C-cell adenocarcinoma developed in an Rb+/-N-ras-/- mouse.
Rb Regulates DNA damage response and cellular senescence through E2F-dependent suppression of N-ras isoprenylation.
No sample metadata fields
View Samples17beta-hydroxysteroid dehydrogenase type12 (HSD17B12) has been demonstrated to be involved in regulation of in situ biosynthesis of estradiol (E2). HSD17B12 expression was reported in breast carcinomas but its functions have remained unknown. Therefore, we examined the correlation between mRNA expression profiles determined by microarray analysis and tissue E2 concentrations obtained from 16 postmenopausal breast carcinoma cases in order to analyze an association of the enzyme expression with intratumoral E2 production. No significant correlations were detected between intratumoral HSD17B12expression and E2 concentration.These findings suggest that the presence of HSD17B12 in carcinoma cells contributes to a development of human breast carcinoma via a pathway other than in situ E2 biosynthesis.
17Beta-hydroxysteroid dehydrogenase type 12 in human breast carcinoma: a prognostic factor via potential regulation of fatty acid synthesis.
Sex, Specimen part
View SamplesA single spermatogonial stem cell can aquire pluripotentiality but that conversion into a pluripotent cell type is accompanied by loss of spermatogenic potential.
Pluripotency of a single spermatogonial stem cell in mice.
No sample metadata fields
View SamplesPurpose:Next-generation sequencing has revolutionized sytems-level celluar pathway analysis. The goals of this study are to compare the U87 cell xenograft GBM mice (U87 cell line) to TWIST1 knock out U87 cell xenograft GBM mice (TWIST1 knock out U87 cell line) using their transcriptomes Overall design: Methods: Investigation of TWIST1 expression on glioblastoma malignancy in vitro and in vivo.
Targeting TWIST1 through loss of function inhibits tumorigenicity of human glioblastoma.
Specimen part, Subject
View SamplesToll-like receptor and RIG-I-like receptor classs may evoke or instruct a distinct type of response that is more reflective of the pathogen encountered. Although this issue may be critical to a better understanding of the regulation of immune responses to microbial infections, it has not been addressed through a direct, side-by-side comparison of the two receptor classes.
Cross-interference of RLR and TLR signaling pathways modulates antibacterial T cell responses.
Treatment
View Samples