Tag Archives: long non-coding RNA

Imprinted Chromatin around DIRAS3 Regulates Alternative Splicing of GNG12-AS1, a Long Noncoding RNA

Imprinted gene clusters are regulated by long noncoding RNAs (lncRNAs), CCCTC binding factor (CTCF)-mediated boundaries, and DNA methylation. DIRAS3 (also known as ARH1 or NOEY1) is an imprinted gene encoding a protein belonging to the RAS superfamily of GTPases and is located within an intron of a lncRNA called GNG12-AS1.

In this study, researchers at Cancer Research UK investigated whether GNG12-AS1 is imprinted and coregulated with DIRAS3. They report that GNG12-AS1 is coexpressed with DIRAS3 in several tissues and coordinately downregulated with DIRAS3 in breast cancers. GNG12-AS1 has several splice variants, all of which initiate from a single transcription start site. In placenta tissue and normal cell lines, GNG12-AS1 is biallelically expressed but some isoforms are allele-specifically spliced. Cohesin plays a role in allele-specific splicing of GNG12-AS1. In breast cancer cell lines with loss of DIRAS3 imprinting, DIRAS3 and GNG12-AS1 are silenced in cis and the remaining GNG12-AS1 transcripts are predominantly monoallelic. The GNG12-AS1 locus, which includes DIRAS3, provides an example of imprinted cotranscriptional splicing and a potential model system for studying the long-range effects of CTCF-cohesin binding on splicing and transcriptional interference.

  • Niemczyk M, Ito Y, Huddleston J, Git A, Abu-Amero S, Caldas C, Moore GE, Stojic L, Murrell A. (2013) Imprinted Chromatin around DIRAS3 Regulates Alternative Splicing of GNG12-AS1, a Long Noncoding RNA. Am J Hum Genet [Epub ahead of print]. [article]

Differential Expression of Long Non-Coding RNAs in the Livers of Female B6C3F1 Mice

The mammalian genome is transcribed into mRNAs that code for protein as well as a broad spectrum of other noncoding (nc) RNA products. Long ncRNAs (lncRNA), defined as ncRNA species > 200 nucleotides long, are emerging as important epigenetic regulators of gene expression that are involved in a spectrum of biological processes of relevance to toxicology.

A team led by researchers at ILS Genomics conducted a gene expression profiling study in the livers of female B6C3F1 mice exposed to the carcinogen furan at 0.0, 1.0, 2.0, (non-carcinogenic doses) and at 4.0, 8.0 mg/kg (carcinogenic doses) for 3 weeks. LncRNA differential expression showed a non-linear dose response with none differentially expressed at 1.0 or 2.0 mg/kg, two lncRNAs at 4.0 mg/kg furan, and 83 at 8 mg/kg, representing 13.3% (83/632) of the total number of differentially expressed transcripts. Among the lncRNAs observed, -two lncRNAs examined showed transcriptional clustering with nearby protein coding genes. LncRNA-p21, is anl anti-sense transcript that is 15 kb downstream from Cdkn1a locus and appears to be co-transcribed with the protein coding gene Cdkn1a at 8.0 mg/kg furan. In a separate independent study, RNA samples from the livers of mice administered benzo(a)pyrene also demonstrated increase levels of Cdkn1a and the antisense lncRNA-p21 transcript. These data demonstrate that lncRNAs are transcriptional targets of furan-exposures associated with levels of furan that are cytotoxic, and induce cell proliferation. In addition, certain lncRNA transcripts are associated with the expression of nearby coding protein genes. The researchers hypothesize that lncRNAs have potential as epigenetic biomarkers of carcinogenic exposures.

  • Recio L, Phillips SL, Maynor T, Waters M, Jackson AF, Yauk CL. (2013) Differential Expression of Long Non-Coding RNAs in the Livers of Female B6C3F1 Mice Exposed to the Carcinogen Furan. Toxicol Sci [Epub ahead of print]. [abstract]

Featured long non-coding RNA: KIR antisense

Human NK cells express cell surface class I MHC receptors (killer cell immunoglobulin-like receptor, KIR) in a probabilistic manner. Previous studies have shown that a distal promoter acts in conjunction with a proximal bidirectional promoter to control the selective activation of KIR genes.

Researchers at SAIC-Frederick report here the presence of an intron 2 promoter in several KIR genes that produce a spliced antisense transcript. This long noncoding RNA (lncRNA) transcript contains antisense sequence complementary to KIR-coding exons 1 and 2 as well as the proximal promoter region of the KIR genes. The antisense promoter contains myeloid zinc finger 1 (MZF-1)-binding sites, a transcription factor found in hematopoietic progenitors and myeloid precursors. The KIR antisense lncRNA was detected only in progenitor cells or pluripotent cell lines, suggesting a function that is specific for stem cells. Overexpression of MZF-1 in developing NK cells led to decreased KIR expression, consistent with a role for the KIR antisense lncRNA in silencing KIR gene expression early in development.

  • Wright PW, Huehn A, Cichocki F, Li H, Sharma N, Dang H, Lenvik TR, Woll P, Kaufman D, Miller JS, Anderson SK. (2013) Identification of a KIR antisense lncRNA expressed by progenitor cells. Genes Immun [Epub ahead of print]. [abstract]

Webinar: Long non-coding RNAs in Development & Disease Progression

Long noncoding RNAs (LncRNAs) are eukaryotic RNA molecules greater than 200 nucleotides in length that have no protein-coding capacity. Recently, LncRNAs have emerged as important factors in gene regulation. The inappropriate expression of some LncRNAs has been demonstrated to cause diseases such as liver cancer and Alzheimer’s.

Ed Davis, Ph.D., Technical Support Specialist at Arraystar, Inc. discusses the biological and medical significance of LncRNAs, as well as about high-throughput LncRNA profiling methods for scientists studying development and the pathogenesis of disease.

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Webinar: Detection of Long Noncoding RNAs by Stellaris FISH Probes

Long non-coding RNAs are now appearing from the genome’s dark matter. Much of what was previously labeled as junk DNA in fact produces non-coding RNA. While non-coding RNAs serve important biological functions, the lack of protein products requires new tools for detection and quantification. To meet this need, Stellaris RNA FISH probes from Biosearch Technologies are now entering laboratories around the world, allowing scientists to expand our understanding of the role of non-coding RNA and to pave the way for future diagnostic and prognostic tests. Here we address the challenges present in designing such probes against long non-coding RNA targets.