DETROIT – Wayne State University School of Medicine Associate Professor of Molecular Medicine, Genetics, and of Neurology Leonard Lipovich, Ph.D., is among a team of international multidisciplinary scientists to contribute to an atlas published today in Nature that reveals how thousands of long non-coding RNAs in humans, once considered genetic “junk,” are directly involved in diseases and other genetic traits.
Lipovich is a member of the WSU Center for Molecular Medicine and Genetics, and has been studying long non-coding RNA genes, or lncRNAs, since the late 1990s.
“Two-thirds of human genes encode lncRNAs, not proteins. However, lncRNAs remain poorly understood, because much of the genomics community has been focusing on the genome and epigenetics, instead of the transcriptome, in the decade and a half since the Human Genome Project was completed,” Lipovich said.
The atlas, which contains 27,919 long non-coding RNAs, summarizes for the first time their expression patterns across the major human cell types and tissues. By intersecting this atlas with genomic and genetic data, results suggest that 19,175 of these RNAs might be functional, hinting that there could be as many – or even more – functional non-coding RNAs than the approximately 20,000 protein-coding genes in the human genome.
While it was once believed that genes regulated biological functions almost exclusively by being transcribed to coding RNAs that were then translated into proteins, it is now known that the picture is much more complex. Studies examining the association between genes and diseases have shown that most disease variants are found outside of protein-coding genes.
For nearly two decades, the Japan-based international FANTOM (Functional Annotation of Mammalian cDNA) Consortium has provided a counterpoint to the mainstream, protein-centric narrative of post-genomic biology, focusing on the transcriptome with an emphasis on ncRNAs. FANTOM catalogued the entire human, including lncRNA, promoterome at a single-nucleotide resolution in 1,000 human and 500 mouse tissues, using cutting-edge Cap Analysis of Gene Expression (CAGE) technology in a study published in Nature in 2014, co-authored by Lipovich.
The FANTOM Consortium, led by RIKEN – Japan's largest research institute for basic and applied research – pioneered the discovery of non-coding RNAs more than a decade ago, revealing the complexity of the transcriptional landscape in mammalian genomes for the first time. Now, the consortium continues to be on the leading edge of studies into the origins and functions of non-coding RNAs. The latest work published today, “An Atlas of Human Long Non-Coding RNAs with Accurate 5’ ends,” (Hon et al 2017, Nature) has generated a comprehensive atlas of human long non-coding RNAs with substantially improved gene models, which allows better assessment of the diversity and functionality of these RNAs. Resources of the lncRNA atlas are available at http://fantom.gsc.riken.jp/cat.
The majority of long non-coding RNAs appear to be generated from enhancer elements, added RIKEN Division of Genomic Technologies Research Scientist Chung-Chau Hon, Ph.D., the paper’s lead author. “It deepens our understanding toward the largely heterogeneous origins of long non-coding RNAs,” he said.
Piero Carninci, Ph.D., deputy director of the RIKEN Center for Life Science Technologies, said, “The improved gene models and the broad functional hints of human long non-coding RNAs derived from this atlas could serve as the Rosetta Stone for us to experimentally investigate their functional relevance, which is ongoing in the upcoming edition of the FANTOM consortium. We anticipate these results would further push the boundary of our understanding towards the functions the non-coding portion of our genome.”
About Wayne State University School of Medicine
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