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

Abstract

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 we 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, we 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, we 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.

Regulation of the ESC transcriptome by nuclear long noncoding RNAs

“…Landmark cDNA cloning efforts and transcriptional interrogation using tiling arrays, together with more recent genome-wide RNA sequencing and chromatin state analyses, have led to the discovery that the majority of the mammalian genome is transcribed to yield tens of thousands of RNA products (Kapranov et al 2002(Kapranov et al , 2007Okazaki et al 2002;Bertone et al 2004;Carninci et al 2005;Cheng et al 2005;Katayama et al 2005;Guttman et al 2009Guttman et al , 2010Khalil et al 2009;Kim et al 2010;Djebali et al 2012; The ENCODE Project Consortium 2012; Hangauer et al 2013). A significant subset of these RNAs are spliced, yielding transcripts >200 nt in length, but without apparent protein coding potential, and are hence referred to as long noncoding RNAs (lncRNAs).…”

Finding function in mystery transcripts

“…In the cautious camp is Michael McManus at the University of California, San Francisco. In 2013, his group mined published data sets of RNA sequences and found tens of thousands of new human lncRNAs, although many were present in cells only in very low amounts 3 . Most of these still need to be followed up, McManus says.…”

Identification and analysis of mouse non-coding RNA using transcriptome data

“…Thousands of lincRNAs are found in mouse (Guttman et al, 2009(Guttman et al, , 2010Liu et al, 2011;Luo et al, 2013;Sigova et al, 2013), human (Cabili et al, 2011;Hangauer et al, 2013;Sigova et al, 2013), chimpanzee (Wetterbom et al, 2010), zebrafish (Pauli et al, 2012;Ulitsky et al, 2011), frog (Tan et al, 2013), nematode (Nam and Bartel, 2012) and Arabidopsis (Liu et al, 2012). Some newly identified lincRNAs have well-validated functions.…”