Author
Listed:
- Matthew J Hangauer
- Ian W Vaughn
- Michael T McManus
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.Author Summary: Much of the human genome is composed of intergenic sequence, the regions between genes. Intergenic sequence was once thought to be transcriptionally silent “junk DNA,” but it has recently become apparent that intergenic regions can be transcribed. However, the scope, nature, and identity of this intergenic transcription remain unknown. Here, by analyzing a large set of RNA-seq data, we found that >85% of the genome is transcribed, allowing us to generate a comprehensive catalog of an important class of intergenic transcripts: long intergenic noncoding RNAs (lincRNAs). We found that the genome encodes far more lincRNAs than previously known. A key question in the field is whether these intergenic transcripts are functional or transcriptional noise. We found that the lincRNAs we identified have many characteristics that are inconsistent with noise, including specific regulation of their expression, the presence of conserved sequence and evidence for regulated processing. Furthermore, these lincRNAs are strongly enriched with intergenic sequences that were previously known to be functional in human traits and diseases. This study provides an essential framework from which the functional elements in intergenic regions can be identified and characterized, facilitating future efforts toward understanding the roles of intergenic transcription in human health and disease.
Suggested Citation
Matthew J Hangauer & Ian W Vaughn & Michael T McManus, 2013.
"Pervasive Transcription of the Human Genome Produces Thousands of Previously Unidentified Long Intergenic Noncoding RNAs,"
PLOS Genetics, Public Library of Science, vol. 9(6), pages 1-13, June.
Handle:
RePEc:plo:pgen00:1003569
DOI: 10.1371/journal.pgen.1003569
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Cited by:
- Zhantao Shao & Jack Hu & Allison Jandura & Ronit Wilk & Matthew Jachimowicz & Lingfeng Ma & Chun Hu & Abby Sundquist & Indrani Das & Phillip Samuel-Larbi & Julie A. Brill & Henry M. Krause, 2024.
"Spatially revealed roles for lncRNAs in Drosophila spermatogenesis, Y chromosome function and evolution,"
Nature Communications, Nature, vol. 15(1), pages 1-13, December.
- Haiqing Xu & Chuan Li & Chuan Xu & Jianzhi Zhang, 2023.
"Chance promoter activities illuminate the origins of eukaryotic intergenic transcriptions,"
Nature Communications, Nature, vol. 14(1), pages 1-11, December.
- Hrant Hovhannisyan & Toni Gabaldón, 2021.
"The long non-coding RNA landscape of Candida yeast pathogens,"
Nature Communications, Nature, vol. 12(1), pages 1-13, December.
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