Tag Archives: lincRNAs

vlincRNAs: very long intergenic non-coding RNAs

The function of the non-coding portion of the human genome remains one of the most important questions of our time. Its vast complexity is exemplified by the recent identification of an unusual and notable component of the transcriptome - very long intergenic non-coding RNAs, termed vlincRNAs.

Here a team led by researchers from the St. Laurent Institute identify 2,147 vlincRNAs covering 10 percent of our genome. They show they are present not only in cancerous cells, but also in primary cells and normal human tissues, and are controlled by canonical promoters. Furthermore, vlincRNA promoters frequently originate from within endogenous retroviral sequences. Strikingly, the number of vlincRNAs expressed from endogenous retroviral promoters strongly correlates with pluripotency or the degree of malignant transformation. These results suggest a previously unknown connection between the pluripotent state and cancer via retroviral repeat-driven expression of vlincRNAs. Finally, they show that vlincRNAs can be syntenically conserved in humans and mouse and their depletion using RNAi can cause apoptosis in cancerous cells.

  • St Laurent G 3rd, Shtokalo D, Dong B, Tackett MR, Fan X, Lazorthes S, Nicolas E, Sang N, Triche TJ, McCaffrey TA, Xiao W, Kapranov P. (2013) VlincRNAs controlled by retroviral elements are a hallmark of pluripotency and cancer. Genome Biol 14(7), R73. [abstract]

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

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

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]

Systematic study of human long intergenic non-coding RNAs and their impact on cancer

The functional impact of several long intergenic non-coding RNAs (lincRNAs) has been characterized in previous studies. However, it is difficult to identify lincRNAs on a large-scale and to ascertain their functions or predict their structures in laboratory experiments because of the diversity, lack of knowledge and specificity of expression of lincRNAs. Furthermore, although there are a few well-characterized examples of lincRNAs associated with cancers, these are just the tip of the iceberg owing to the complexity of cancer.

Here, by combining RNA-Seq data from several kinds of human cell lines with chromatin-state maps and human expressed sequence tags, researchers at Jilin University, China successfully identified more than 3000 human lincRNAs, most of which were novel. Subsequently, they predicted the functions of 105 lincRNAs based on a coding-non-coding gene co-expression network. Finally, they propose a genetic mediator and key regulator model to unveil the subtle relationships between lincRNAs and lung cancer. Twelve lincRNAs may be principal players in lung tumorigenesis.

The present study combines large-scale identification and functional prediction of human lincRNAs, and is a pioneering work in characterizing cancer-associated lincRNAs by bioinformatics.

  • Sun L, Luo H, Liao Q, Bu D, Zhao G, Liu C, Liu Y, Zhao Y. (2013) Systematic study of human long intergenic non-coding RNAs and their impact on cancer. Sci China Life Sci [Epub ahead of print]. [abstract]

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  • non examples of genes

Twice as many human and mouse lincRNAs than protein-coding genes

Genome analysis of humans and other mammals reveals a surprisingly small number of protein-coding genes, only slightly over 20,000 (although the diversity of actual proteins is substantially augmented by alternative transcription and alternative splicing). Recent analysis of the mammalian genomes and transcriptomes, in particular, using the RNAseq technology, shows that, in addition to protein-coding genes, mammalian genomes encode many long non-coding RNAs. For some of these transcripts, various regulatory functions have been demonstrated, but on the whole the repertoire of long non-coding RNAs remains poorly characterized. Scientists at National Center for Biotechnology Information, NIH compared the identified long intergenic non-coding (linc)RNAs from human and mouse, and employed a specially developed statistical technique to estimate the size and evolutionary conservation of the human and mouse lincRNomes. The estimates show that there are at least twice as many human and mouse lincRNAs than there are protein-coding genes. Moreover, about two third of the lincRNA genes appear to be conserved between human and mouse, implying thousands of conserved but still uncharacterized functions.

Managadze D, Lobkovsky AE, Wolf YI, Shabalina SA, Rogozin IB, Koonin EV. (2013) The Vast, Conserved Mammalian lincRNome. PLoS Comput Biol 9(2):e1002917. [article]

Incoming search terms:

  • lincrna database