Human Transcribed Ultraconserved regions (T-UCRs) are long noncoding RNAs (LncRNAs) that are transcribed from 481 ultraconserved regions (UCRs) in the human genome (Braconi et al., 2011; Calin et al., 2007; Esteller, 2011; Lujambio et al., 2010). Recent genome-wide expression profiling studies demonstrated that some T-UCRs are aberrantly expressed in leukemia and several solid tumors, such as neuroblastoma (Braconi et al., 2011; Calin et al., 2007; Lujambio et al., 2010, Mestdagh et al., 2010). These results offer promise for the use of T-UCR expression patterns in the diagnosis and prognosis of specific human cancers.
The Arraystar Human T-UCR Microarray 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 Microarray 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 Microarray Service.
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• The annotation of UCR information in current databases is outdated.
• 481 UCRs and their flanking regions using 60nt probes tiled at 40bp spacing: Enables the accurate detection and discovery of potentially novel T-UCRs.
• 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.
• 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.
• 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.
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.
ReferencesBraconi, C., Valeri, N., Kogure, T., Gasparini, P., Huang, N., Nuovo, G.J., Terracciano, L., Croce, C.M., and Patel, T. (2011). Expression and functional role of a transcribed noncoding RNA with an ultraconserved element in hepatocellular carcinoma. Proc Natl Acad Sci U S A 108, 786-791.
Calin, G.A., Liu, C.G., Ferracin, M., Hyslop, T., Spizzo, R., Sevignani, C., Fabbri, M., Cimmino, A., Lee, E.J., Wojcik, S.E., et al. (2007). Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer Cell 12, 215-229.
Esteller, M. (2011). Non-coding RNAs in human disease. Nat Rev Genet 12, 861-874.
Lujambio, A., Portela, A., Liz, J., Melo, S.A., Rossi, S., Spizzo, R., Croce, C.M., Calin, G.A., and Esteller, M. (2010). CpG island hypermethylation-associated silencing of non-coding RNAs transcribed from ultraconserved regions in human cancer. Oncogene 29, 6390-6401.
Mestdagh, P., Fredlund, E., Pattyn, F., Rihani, A., Van Maerken, T., Vermeulen, J., Kumps, C., Menten, B., De Preter, K., Schramm, A., et al. (2010). An integrative genomics screen uncovers ncRNA T-UCR functions in neuroblastoma tumours. Oncogene 29, 3583-3592.