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

By M. Hangauer, Ian W. Vaughn, Michael T. McManus. PLoS Genetics, 2013

722 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/636dec7febfd0f488eef005cf2b34fc46ad855d9

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Citations in the corpus

Non-coding RNA: what is functional and what is junk? (2015, neutral): “…own estimates, fewer than 1,000 lncRNAs are present at greater than one copy per cell in the typical human tissue culture cell line (Djebali et al., 2012; Palazzo and Gregory, 2014), although some other estimates have determined that the levels may be substantially higher (Hangauer et al., 2013).”
Regulation of mammalian nucleotide metabolism and biosynthesis (2015, background): “Enzyme names: (1) carbamoyl phosphate synthase II (CPSII); (2) aspartate transcarbamoylase (ATCase); (3) carbamoyl aspartate dehydratase = dihydroorotase [CAD encodes enzymes 1 + 2 + 3]; (4) dihydroorotate dehydrogenase; (5) orotate phosphoribosyltransferase; (6) orotidine-5-phosphate decarboxylase ”
Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer (2016, background): “Production and hosting by Elsevier B.V. on behalf of Beijing Institute of Genomics, Chinese Academy of Scie Genetics Society of China.”
Single-cell RNA-seq: advances and future challenges (2014, positive): “It is now clear that eukaryotic genomes are pervasively transcribed; for example, while protein-coding genes constitute less than 2% of the human genome, more than 80% of its re-* gions may be transcribed (13).”
Transcriptional and Post-transcriptional Gene Regulation by Long Non-coding RNA (2017, background): “Many but not all lncRNAs are polyadenylated, and there is evidence indicating that many lncRNAs exist in both polyadenylated and nonpolyadenylated forms (termed bimorphic) [3].”