The ultraconserved regions (UCR) are composed of sequences (> 200 bp) that are absolutely conserved and 100% identical across the genomes of distant species, many of which transcribe a category of long non-coding RNAs (T-UCR) assumed to be biologically indispensible[1-4].Human Transcribed Ultraconserved regions (T-UCRs) are long noncoding RNAs (LncRNAs) that are transcribed from 481 ultraconserved regions (UCRs) in the human genome [1-4]. Recent genome-wide expression profiling studies demonstrated that some T-UCRs are aberrantly expressed in leukemia and several solid tumors, such as neuroblastoma [1-3,5]. These results offer promise for the use of T-UCR expression patterns in the diagnosis and prognosis of specific human cancers[1-7].
Challenges for T-UCR Studies
• Previously, there has been no systematic discovery platform for novel T-UCRs
• Detection of potential T-UCRs can be inaccurate due to difficulties in designing specific probes
• Convenient tools to reveal the putative functional relationships between T-UCRs and their proximal protein-coding genes have been unavailable
• The annotation of UCR information in current databases is outdated.
The Arraystar Human T-UCR Array is engineered to profile the global expression of human T-UCRs. 481 UCRs, each flanked by an additional 1kb at each end, are tiled by strand-specific probes at 40bp resolution, to facilitate accurate T-UCR detection and novel T-UCR discovery. Further, the array carries specific exon or splice junction probes to reliably and accurately detect 153 potential T-UCRs, which have been collected from authoritative databases such as Refseq, UCSC knowngenes, and Ensembl. In addition to T-UCR detection, the Arraystar Human T-UCR Array profiles the expression of 1,518 lncRNAs and 2,261 mRNAs whose transcription units (TU) overlap UCRs in either the sense or antisense orientation. Finally, 1,809 genes located within 500 kb of UCRs are represented by gene-specific probes, which could potentially reveal any putative functional relationships between T-UCRs and their proximal protein-coding genes. This microarray is available only through Arraystar's T-UCR Array Service.
References1. Braconi C. et al. (2011) "Expression and functional role of a transcribed noncoding RNA with an ultraconserved element in hepatocellular carcinoma." PNAS 108(2):786-91 [PMID: 21187392]
2. Calin G.A. et al. (2007) "Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas." Cancer Cell 12(3):215-29 [PMID: 17785203]
3. Esteller M. (2011) "Non-coding RNAs in human disease." Nat. Rev. Genet. 12(12):861-74 [PMID: 22094949]
4. Lujambio A. et al. (2010) "CpG island hypermethylation-associated silencing of non-coding RNAs transcribed from ultraconserved regions in human cancer." Oncogene 29(48):6390-401 [PMID: 20802525]
5. Mestdagh P. et al. (2010) "An integrative genomics screen uncovers ncRNA T-UCR functions in neuroblastoma tumours." Oncogene 29(24):3583-92 [PMID: 20383195]
6. Scaruffi P. et al. (2009) "Transcribed-Ultra Conserved Region expression is associated with outcome in high-risk neuroblastoma." BMC Cancer 9:441 [PMID: 20003513]
7. Fassan M. et al. (2014) "Transcribed ultraconserved noncoding RNAs (T-UCR) are involved in Barrett's esophagus carcinogenesis." Oncotarget 5(16):7162-71 [PMID: 25216530]
• 481 UCRs and their flanking regions using 60nt probes tiled at 40bp spacing: Enables the accurate detection and discovery of potentially novel T-UCRs. Learn more>
• Comprehensive and Reliable potential T-UCR collection: Detects 153 potential T-UCRs predicted from the most updated transcriptome databases, such as RefSeq, UCSC knowngenes, and Ensembl. Learn more>
• Accurate detection of RNA transcripts overlapping UCR loci and UCR-proximal genes: Helps researchers uncover potentially interesting functional relationships between T-UCRs and nearby protein-coding genes. Learn more>
• Detailed annotation of UCRs, T-UCRs, and their relationships with cancer-associated genomic regions (CAGRs): Aids cancer researchers in the identification of potentially important biomarkers for diagnosis and prognosis. Learn more>
Total number of probes: 60,887
Probe length: 60 mer
Labeling method: Random priming. Generates Cy3- or Cy5-labeled antisense RNAs along the entire length of the transcript without 3' bias.
|UCRs and their extended regions
|481 UCRs with additional 1kb of sequence flanking each end. Strand-specific probes tiled at 40 bp resolution.
|Potential T-UCRs (long non-coding RNAs, collected from authoritative databases, which overlap UCRs in sense or antisense direction)
|153 potential T-UCRs collected from reliable databases (Refseq, UCSC knowngene, Ensembl, etc.). Probes target specific exons or splice junctions, to accurately and reliably identify T-UCR transcripts.
|RNA transcripts (LncRNAs and mRNAs) whose transcription units (TUs) overlap UCRs
|Include LncRNAs (1,528) and mRNAs (2,261) from NCBI Refseq, UCSC known Gene 5, Ensembl 37.64, and GenBank. Transcription units (TU) overlap with UCRs.
|1,809 protein-coding genes located within 500 kb of UCRs
|20 housekeeping genes (such as ACTB, GAPDH, UBC, and RPS18) serving as internal positive controls.
|60 DNA segments, the sequences of which are not found in the human genome, serving as internal negative controls.
Arraystar's Human T-UCR Array is available only through our T-UCR Array service. We provide full-service T-UCR array profiling, from sample preparation to in-depth data analysis. Our step-by-step quality controls are designed to ensure you get the most reliable results. Just send us your samples, and we'll do the rest!
Please refer to Sample Submission for details of how to get your project started.
• RNA isolation (Optional)
• RNA QC
• cDNA synthesis
• Target preparation by labeling with Cy3
• Array hybridization, washing, and scanning
• Data extraction, analysis and summarization
Arraystar's experienced scientists have the expertise in microarray platform technology and intimate knowledge of T-UCR. We apply the state of the art methods for processing, normalization, analysis, and interpretation of the profiling data. In addition to the UCR and T-UCR sequences, the array profiles and analyzes their extended regions and associated genes. Differentially expressed protein coding genes under potential T-UCR regulation are subjected to gene ontology and pathway analysis to infer biological functions.
T-UCR expression analysis
The expression values and the differential expression are analyzed by scatter-plots, volcano plots, hierarchical clustering heat maps, magnitude of changes and statistical tests. The standard analyses are also included for the following annotated array features.
Novel transcribed Regions in UCRs and their Extended Regions
Most of the T-UCRs have not been well characterized for their transcriptional units so far. 481 UCRs, each flanked by an additional 1kb at each end, are tiled by strand-specific probes at 40bp resolution to discover and define their transcripts.
LncRNA and mRNA transcripts whose transcription units overlap UCRs
The array analyzes thousands of lncRNAs and mRNAs whose transcription units (TU) overlap UCRs in either sense or antisense orientation, which may be regulated post-transcriptionally by the T-UCR, such as alternative splicing and mRNA processing and differentially expressed between cancer and normal tissues.
Intergenic UCRs, along with the expressed T-UCR transcripts, may act as tissue-specific enhancers that regulate distant gene transcription in long range in cis. Thousands of proximal genes located within 500 kb of UCRs are profiled and annotated to reveal such functional relation.
Long Noncoding RNA uc.173 Promotes Renewal of the Intestinal Mucosa by Inducing Degradation of MicroRNA 195. Xiao L, et al. Gastroenterology, 2017
Noncoding Transcribed Ultraconserved Region (T-UCR) uc.261 Participates in Intestinal Mucosa Barrier Damage in Crohn's Disease. Qian X X, et al. inflammatory bowel diseases, 2016