Search Results for: incrna
It is now well-established that noncoding regions of the genome have a vital role to play in gene expression. Genome-wide approaches have led to the identification of an abundance of noncoding RNAs, from microRNAs to long non-coding RNAs (lncRNAs). LncRNAs were initially discovered in the 1980’s but the extent of their transcription was only realized over twenty years later with the advent of improved high-throughput sequencing technologies. Subsequent research has revealed the breadth of cellular processes they are involved in. Maite Huarte from the University of Navarra, Spain and colleagues probe how the novel lncRNA Pint is a target of p53 – a transcription factor that is central to cellular homeostasis and tumour suppression. Huarte explains more about their findings, published in a recent Genome Biology study, that demonstrates how Pint, p53 and epigenetic silencing are all connected.
Expression and regulation of intergenic long noncoding RNAs during T cell development and differentiation
Although intergenic long noncoding RNAs (lincRNAs) have been linked to gene regulation in various tissues, little is known about lincRNA transcriptomes in the T cell lineages. Here researchers at the National Institutes of Health identified 1,524 lincRNA clusters in 42 T cell samples, from early T cell progenitors to terminally differentiated helper T cell subsets. Their analysis revealed highly dynamic and cell-specific expression patterns for lincRNAs during T cell differentiation. These lincRNAs were located in genomic regions enriched for genes that encode proteins with immunoregulatory functions. Many were bound and regulated by the key transcription factors T-bet, GATA-3, STAT4 and STAT6. They found that the lincRNA LincR-Ccr2-5’AS, together with GATA-3, was an essential component of a regulatory circuit in gene expression specific to the TH2 subset of helper T cells and was important for the migration of TH2 cells.
- Hu G, Tang Q, Sharma S, Yu F, Escobar TM, Muljo SA, Zhu J, Zhao K. (2013) Expression and regulation of intergenic long noncoding RNAs during T cell development and differentiation. Nat Immunol [Epub ahead of print]. [abstract]
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.
Now, 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]
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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]
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- A Long Noncoding RNA Mediates Both Activation and Repression of Immune Response Genes
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.
- 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]
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- encode lincRNA database