Antisense long non-coding (aslnc)RNAs represent a substantial part of eukaryotic transcriptomes that are, in yeast, controlled by the Xrn1 exonuclease. Nonsense-Mediated Decay (NMD) destabilizes the Xrn1-sensitive aslncRNAs (XUT), but what determines their sensitivity remains unclear. We report that 3’ single-stranded (3’-ss) extension mediates XUTs degradation by NMD, assisted by the Mtr4 and Dbp2 helicases. Single-gene investigation, genome-wide RNA analyses and double-stranded (ds)RNA mapping revealed that 3''-ss extensions discriminate the NMD-targeted XUTs from stable lncRNAs. Ribosome profiling showed that XUT are translated locking them for NMD activity. Interestingly, mutants of the Mtr4 and Dbp2 helicases accumulated XUTs, suggesting that dsRNA unwinding is a critical step for degradation. Indeed, expression of anti-complementary transcripts protects cryptic intergenic lncRNAs from NMD. Our results indicate that aslncRNAs form dsRNA that are only translated and targeted to NMD if dissociated by Mtr4 and Dbp2. We propose that NMD buffers genome expression by discarding pervasive regulatory transcripts. Overall design: Strand-specific transcriptome analysis of biological replicates (1) of WT and xrn1-delta cells of the S288C, W303 and SK1 (n & 2n) genetic background of S. cerevisiae; (2) of WT, dcp2-7 and upf1-delta cells; (3) of WT, xrn1-delta and dcp2-7 cells upon treatment of total RNA with Terminator 5''-Phosphate-Dependent Exonuclease. This record also contains CAGE-Seq analysis in wild-type and decapping-deficient cells of the budding yeast S. cerevisiae.
Nonsense-Mediated Decay Restricts LncRNA Levels in Yeast Unless Blocked by Double-Stranded RNA Structure.
Subject
View SamplesAvian coccidiosis is a major disease of poultry caused by the intestinal protozoa Eimeria. Aviagen line A and line B birds show differential susceptibility to Eimeria infection, with line B birds exhibiting higher lesion scores and mortality. The objective of this study was to examine differential intestinal gene expression between line A and B chicks in response to a challenge with Eimeria maxima. Following challenge with 1 x 10^4 oocysts/chick, greater than 40% of line A chicks had lesion scores of 0 to 1 (on 0 to 4 scale), similar to controls. In contrast, all line B challenged chicks at this same dose had lesion scores of 2 to 4.
An antimicrobial peptide is downregulated in the small intestine of Eimeria maxima-infected chickens.
Specimen part
View SamplesWe used microarrays to detail the global programme of gene expression upon the over-expression of seven different differentiation-associated, E1A-regulated microRNAs.
Differentiation-associated microRNAs antagonize the Rb-E2F pathway to restrict proliferation.
Cell line
View SamplesProliferating C2C12 myoblasts were induced to differentiate into myotubes and then infected with adenovirus expressing E1A (Ad-E1A), which induces cell cycle re-entry and dedifferentiation.
Differentiation-associated microRNAs antagonize the Rb-E2F pathway to restrict proliferation.
Specimen part, Cell line, Treatment, Time
View SamplesIdentify genes in the aorta whose expressions under genetic regulation in the Hybrid Mouse Diversity Panel (HMDP). The HDMP is comprised of classical inbred and recombinant inbred wild-type mice. The RMA values of genes were used for genome-wide association as described in Bennett et al. Genome Research 2010 (PMID 20054062). These data were used to identify candidate genes at loci associated with atherosclerosis.
High-resolution association mapping of atherosclerosis loci in mice.
Sex, Age, Specimen part
View SamplesTranscriptomic analysis of fresh breast cancer tissue versus normal tissues. The Study comprising 45 Saudi-Arabian subjects was designed to take advantage of transcriptomics to prospectively explore the roles of lifestyle and genetic susceptibility in the occurrence of breast cancer.
Expression of matrix metalloproteinases (MMPs) in primary human breast cancer: MMP-9 as a potential biomarker for cancer invasion and metastasis.
Specimen part, Disease stage
View SamplesThis work focuses on understanding the molecular basis of the immune dysfunctions in Idiopathic CD4+ T cells lymphocytopenia (ICL). ICL is a rare haematological disorder of unknown origin, characterized by a profound and persistent CD4+ T-cell defect, which predisposes to life threatening opportunistic infections very similar to those seen in AIDS. To analyse more in depth the functional pathways involved in ICL pathogenesis, we conducted gene expression profiling of CD4+ T-cells isolated from blood samples from ICL, sarcoidosis and healthy individuals. Our analyses have revealed specific CD4+ T-cells gene expression signatures in ICL associated with defective TCR activation threshold, expansion of the Treg-cell compartment and interestingly with accelerated immune aging.
DUSP4-mediated accelerated T-cell senescence in idiopathic CD4 lymphopenia.
Sex
View SamplesThe endoplasmic reticulum (ER) is the site of secretory lipoprotein production and de novo cholesterol synthesis, yet little is known about how these activities are coordinated with each other, or with the activity of the COPII machinery, which transports ER cargo to the Golgi. The Sar1B component of this machinery is mutated in Chylomicron Retention Disorder, establishing that this Sar1 isoform secures delivery of dietary lipids into the circulation.
The endoplasmic reticulum coat protein II transport machinery coordinates cellular lipid secretion and cholesterol biosynthesis.
No sample metadata fields
View SamplesIn this study, we analyzed the impact of a mutation in the wrn-1 gene compared to wild type worms and the dietary supplementation of vitamin C on the global mRNA expression of the whole C. elegans by the RNA-seq technology. Overall design: Whole C. elegans mRNA profiles at the L4 stage of wild type and wrn-1(gk99) mutant animals treated with or without 10 mM ascorbate were generated by deep sequencing, in triplicate, using the HiSeq 2000 machine form Illumina. Detailed statistics on the quality of the reads were calculated with FastQC (http://www.bioinformatics.babraham.ac.uk/projects/fastqc/). The 50 base pairs raw sequences were aligned on the C. elegans ce10/W220 genome with TopHat using the Ensembl annotations provided with the Illumina iGenomes. The htseq-count software (http://www-huber.embl.de/users/anders/HTSeq) was used to count the number of reads aligned to each gene. These counts were then normalized relative to the sequencing depth with DESeq.
Expression profile of Caenorhabditis elegans mutant for the Werner syndrome gene ortholog reveals the impact of vitamin C on development to increase life span.
Specimen part, Treatment, Subject
View SamplesExperiment: Expression profiling in breast cancer brain metastases (BC) compared to breast cancers (BC) and primary brain tumors (prBT). The objectives are to identify expression profiles that are specific to BCBM in order to identify new molecular biomarkers. The characterization of the BCBM samples included adjacent genetic techniques.
Comprehensive molecular biomarker identification in breast cancer brain metastases.
Sex, Specimen part, Disease stage
View Samples