Search Results for: incrna

Clinical Significance of Long Intergenic Noncoding RNA-p21 in Colorectal Cancer

Long intergenic noncoding RNAs (lincRNAs) have been shown to be novel regulators for both transcription and posttranscriptional/translation. One of them, lincRNA-p21, was regulated by p53 and contributed to apoptosis in mouse embryonic fibroblasts. However, the impact of such regulation on colorectal cancer (CRC) remains to be determined.

lncRNANow, researchers at the Stony Brook University have discovered that the expression level of lincRNA-p21 is increased by elevated wild-type p53 induced by nutlin-3 in HCT-116 colon cancer cells. The expression level of lincRNA-p21 was significantly (P = .0208) lower in CRC tumor tissue when compared with the paired normal tissue from the same patient. There was no significant correlation of lincRNA-p21 with p53 status (wild-type vs. mutant). Tumors in the rectum showed a higher level of lincRNA-p21 than tumors in the colon. In addition, lincRNA-p21 in patients with stage III tumors was significantly higher than in those with stage I tumors. Elevated levels of lincRNA-p21 were significantly associated with higher pT and vascular invasion.

These results indicate that lincRNA-p21 may contribute to CRC disease progression.

  • Zhai H, Fesler A, Schee K, Fodstad O, Flatmark K, Ju J. (2013) Clinical Significance of Long Intergenic Noncoding RNA-p21 in Colorectal Cancer. Clin Colorectal Cancer [Epub ahead of print]. [abstract]

Incoming search terms:

  • lincRNA-p21

A Long Noncoding RNA Mediates Both Activation and Repression of Immune Response Genes

lncRNA

An inducible program of inflammatory gene expression is central to antimicrobial defenses. Signal-dependent activation of transcription factors, transcriptional co-regulators, and chromatin modifying factors collaborate to control this response. Here, researchers from the University of Massachusetts Medical School identify a long noncoding RNA that acts as a key regulator of this inflammatory response. Pattern recognition receptors such as the Toll-like receptors induce the expression of numerous lncRNAs. One of these, lincRNA-Cox2 mediates both the activation and repression of distinct classes of immune genes. Transcriptional repression of target genes is dependent on interactions of lincRNA-Cox2 with heterogeneous nuclear ribonucleoprotein A/B and A2/B1. Collectively, these studies unveil a central role of lincRNA-Cox2 as a broad acting regulatory component of the circuit that controls the inflammatory response.

  • Carpenter S, Atianand M, Aiello D, Ricci EP, Gandhi P, Hall LL, Byron M, Monks B, Henry-Bezy M, Lawrence JB, O’Neill LA, Moore MJ, Caffrey DR, Fitzgerald KA. (2013) A Long Noncoding RNA Mediates Both Activation and Repression of Immune Response Genes. Science [Epub ahead of print]. [abstract]

Incoming search terms:

  • lincrna-cox2
  • A Long Noncoding RNA Mediates Both Activation and Repression of Immune Response Genes

Ribosome Profiling Provides Evidence that Large Noncoding RNAs Do Not Encode Proteins

Large noncoding RNAs are emerging as an important component in cellular regulation. Considerable evidence indicates that these transcripts act directly as functional RNAs rather than through an encoded protein product. However, a recent study of ribosome occupancy reported that many large intergenic ncRNAs (lincRNAs) are bound by ribosomes, raising the possibility that they are translated into proteins.

Here, researchers from the Broad Institute of MIT and Harvard show that classical noncoding RNAs and 5′ UTRs show the same ribosome occupancy as lincRNAs, demonstrating that ribosome occupancy alone is not sufficient to classify transcripts as coding or noncoding. Instead, they  define a metric based on the known property of translation whereby translating ribosomes are released upon encountering a bona fide stop codon. They show that this metric accurately discriminates between protein-coding transcripts and all classes of known noncoding transcripts, including lincRNAs. Taken together, these results argue that the large majority of lincRNAs do not function through encoded proteins.

lncRNA

  • Guttman M, Russell P, Ingolia NT, Weissman JS, Lander ES. (2013) Ribosome Profiling Provides Evidence that Large Noncoding RNAs Do Not Encode Proteins. Cell  154(1), 240-51. [abstract]

Incoming search terms:

  • encode lincRNA database

Seminar – Measurement and analysis of mRNAs and long non-coding RNAs using RNA-Seq

lncRNA

H3ABioNet – Pan African Bioinformatics Network for H3Africa

These one day courses are designed for scientists and clinicians with little or no experience in next generation sequencing. The courses aim to provide the experimental and bioinformatics skills required to prepare samples, quantify the levels of mRNA/long-non-coding RNA (RNAseq) or exon/DNA (DNAseq) expresion. We assume that sequencing will be performed by an external provider and will provide advice in this area. The courses are computer based and will involve a combination of presentations/exercises to analysis ‘actual’ next generation sequencing data using publically (free) available programmes.
Content:

  • Overview on mRNAs and long non-coding RNAs
  • Introduction to RNA databases (Ensembl, RefSeq, GenBank and human lincRNA catalogue)
  • RNA isolation techniques and quality assessment
  • Overview of next generation sequencing platforms (ABI Solid, Illumina Solexa, Life Technologies Ion Torrent)
  • Introduction to data file formats (FASTA, FASTQ, SAM, BAM, GTF and BED files)
  • Mapping of RNA data onto a reference genome using Tophat
  • Quantification of known RNA species using CuffDiff
  • Identification and quantification of novel RNA transcripts using CuffLinks
  • Visualisation and analysis of sequencing data using the IGV genome browsers
  • Functional annotation using DAVID pathway analysis

Course Trainers: Dr Nick Ilott (University of Oxford) and Prof Mark Lindsay (University of Bath)
Dates and location:
Tuesday 9th July 2013 – IMG Training Rooms, Near Liverpool Street Station, London

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Incoming search terms:

  • lncrna isolation

Pervasive Transcription of the Human Genome Produces Thousands of Previously Unidentified Long Intergenic Noncoding RNAs

lncRNA

Known protein coding gene exons compose less than 3% of the human genome. The remaining 97% is largely uncharted territory, with only a small fraction characterized. The recent observation of transcription in this intergenic territory has stimulated debate about the extent of intergenic transcription and whether these intergenic RNAs are functional.

Here, researchers at the University of California, San Francisco directly observed with a large set of RNA-seq data covering a wide array of human tissue types that the majority of the genome is indeed transcribed, corroborating recent observations by the ENCODE project. Furthermore, using de novo transcriptome assembly of this RNA-seq data, they found that intergenic regions encode far more long intergenic noncoding RNAs (lincRNAs) than previously described, helping to resolve the discrepancy between the vast amount of observed intergenic transcription and the limited number of previously known lincRNAs. In total, they identified tens of thousands of putative lincRNAs expressed at a minimum of one copy per cell, significantly expanding upon prior lincRNA annotation sets. These lincRNAs are specifically regulated and conserved rather than being the product of transcriptional noise. In addition, lincRNAs are strongly enriched for trait-associated SNPs suggesting a new mechanism by which intergenic trait-associated regions may function. These findings will enable the discovery and interrogation of novel intergenic functional elements.

  • Hangauer MJ, Vaughn IW, McManus MT. (2013) Pervasive Transcription of the Human Genome Produces Thousands of Previously Unidentified Long Intergenic Noncoding RNAs. PLoS Genet 9(6), e1003569. [article]