CRNDE: A Long Non-Coding RNA Involved in CanceR, Neurobiology, and DEvelopment - PubMed (original) (raw)

CRNDE: A Long Non-Coding RNA Involved in CanceR, Neurobiology, and DEvelopment

Blake C Ellis et al. Front Genet. 2012.

Abstract

CRNDE is the gene symbol for Colorectal Neoplasia Differentially Expressed (non-protein-coding), a long non-coding RNA (lncRNA) gene that expresses multiple splice variants and displays a very tissue-specific pattern of expression. CRNDE was initially identified as a lncRNA whose expression is highly elevated in colorectal cancer, but it is also upregulated in many other solid tumors and in leukemias. Indeed, CRNDE is the most upregulated lncRNA in gliomas and here, as in other cancers, it is associated with a "stemness" signature. CRNDE is expressed in specific regions within the human and mouse brain; the mouse ortholog is high in induced pluripotent stem cells and increases further during neuronal differentiation. We suggest that CRNDE is a multifunctional lncRNA whose different splice forms provide specific functional scaffolds for regulatory complexes, such as the polycomb repressive complex 2 (PRC2) and CoREST chromatin-modifying complexes, which CRNDE helps pilot to target genes.

Keywords: 4933436C20Rik; CRNDE; IRX5; cancer; glioma; lncRNA; multipotency; neurogenesis.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Expression of CRNDE in normal adult human cell types. (A) Expression levels were measured on Affymetrix HG-U133 arrays; data from the Body Atlas, Cell Types, at

http://www.nextbio.com

. The median expression across all 67 cell types in the database is shown by the green line. All of the blood cells listed come from peripheral blood. (B) CRNDE expression levels plotted against IRX5 expression levels for each cell type in NextBio. An unreplicated experiment on dental odontoblasts with anomalous outcomes for both genes has been omitted. When spermatozoa are excluded, the two genes show correlated expression (R = 0.72 in linear regression by KaleidaGraph v3.6, Synergy Software).

Figure 2

Figure 2

Human CRNDE gene locus. (A) Nucleotide numbering (top) is for chromosome 16, hg19. Below that is the CRNDE locus, oriented 5′ to 3′ (left to right). Exons are shown as boxes with cyan fill; the most highly conserved regions of the locus, which are intronic, are shown as boxes with olive-green fill. The target regions of the two HG-U133 probesets are shown immediately below the locus baseline. The two RefSeq genes are shown; fully spliced AceView transcripts (not shown) typically commence with just a short segment from the 3′ end of one of the two alternative first exons, E1A and E1B. Evolutionary conservation within the locus is shown for placental mammals (PhyloP) and for vertebrates in general (Multiz alignments). The bottom of this panel shows the expression of CRNDE exons and some intronic regions in normal human tissues, obtained using the Affymetrix Exon Array 1.0; the data for each probeset are color-coded (red, expression higher than the median value across all tissues, green, expression lower than the median). Source of data below locus diagram: UCSC Genome Browser (

http://www.genome.ucsc.edu

), minus-strand display. (B) First exons of CRNDE and IRX5 and the intervening promoter-containing region (∼2 kb) between their transcription start sites. Transcription factor (TF) binding was identified from “Transcription factor Binding Sites by ChIP-seq from ENCODE/HAIB” tracks on UCSC Genome Browser. Regions of strongest binding in HCT116 cells by TFs (listed on the left) are shown by pink shaded boxes. Blue stars indicate the locations of predicted strong TF DNA binding motifs, from the TRANSFAC database (Wingender, 2008).

Figure 3

Figure 3

CRNDE expression in the human brain. (A) Schematic showing the region where CRNDE is expressed in the adult human brain. CRNDE expression (shaded pink) is concentrated in the deep central structures (especially the basal ganglia and adjacent structures), cerebellum, posterior brain stem, and spinal cord. In the CRNDE-expressing region, no attempt has been made to display differences in expression levels between or within structures. (B) Affymetrix Human Exon 1.0 ST microarray expression data from the late mid-fetal human brain, generated by the Sestan Lab at Yale University; these are grouped by the median for each brain region and color-coded as in Figure 2A. The first nine regions are from the neocortical region of the cerebral cortex; PFC, pre-frontal cortex. Data sources:

http://www.molecularbrain.org

, the Allen Human Brain Atlas (Brain Explorer 2), and Sestan Human Brain Atlas (UCSC Genome Browser).

Similar articles

Cited by

References

    1. Anselme I., Laclef C., Lanaud M., Rüther U., Schneider-Maunoury S. (2007). Defects in brain patterning and head morphogenesis in the mouse mutant fused toes. Dev. Biol. 304, 208–22010.1016/j.ydbio.2006.12.025 - DOI - PubMed
    1. Bánfai B., Jia H., Khatun J., Wood E., Risk B., Gundling W. E., Jr., et al. (2012). Long noncoding RNAs are rarely translated in two human cell lines. Genome Res. 22, 1646–165710.1101/gr.134767.111 - DOI - PMC - PubMed
    1. Bao S., Wu Q., McLendon R. E., Hao Y., Shi Q., Hjelmeland A. B., et al. (2006). Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444, 756–76010.1038/nature05236 - DOI - PubMed
    1. Bernard D., Prasanth K. V., Tripathi V., Colasse S., Nakamura T., Xuan Z., et al. (2010). A long nuclear-retained non-coding RNA regulates synaptogenesis by modulating gene expression. EMBO J. 29, 3082–309310.1038/emboj.2010.199 - DOI - PMC - PubMed
    1. Bond A. M., Vangompel M. J., Sametsky E. A., Clark M. F., Savage J. C., Disterhoft J. F., et al. (2009). Balanced gene regulation by an embryonic brain ncRNA is critical for adult hippocampal GABA circuitry. Nat. Neurosci. 12, 1020–102710.1038/nn.2371 - DOI - PMC - PubMed

LinkOut - more resources