A team led by researchers at the Center for Medical Genetics at Ghent University in Belgium has constructed the most comprehensive atlas of the human transcriptome to date. The atlas, which includes small and polyA RNA, as well as total RNA from 300 human tissues and cell lines, makes a particularly important contribution in the amount of non-coding RNAs (ncRNAs) included in the atlas. Never before such a comprehensive effort was undertaken to characterize all RNA-molecules in human cells and tissues.
The work is published in Nature Biotechnology in the paper, “The RNA Atlas expands the catalog of human non-coding RNAs.” The RNA Atlas is the result of more than five years of hard work to further unravel the complexity of the human transcriptome.
“There have been other projects to catalog our transcriptome but the RNA-Atlas project is unique because of the applied sequencing methods,” said Pieter Mestdagh, PhD, professor at the faculty of medicine and health sciences and co-founder of CRIG (Cancer Research Institute Ghent) from the Center for Medical Genetics at Ghent University. “Not only did we look at the transcriptome of as many as 300 human cell and tissue types, but most importantly, we did so with three complementary sequencing technologies, one aimed at small RNAs, one aimed at polyadenylated (polyA) RNAs, and a technique called total RNA sequencing.”
This last sequencing technology led to the discovery of thousands of novel noncoding RNA genes, including a novel class of non-polyadenylated single exon genes and many new circular RNAs. The authors noted that their report includes “thousands of previously uncharacterized RNAs, increasing the number of documented ncRNAs by approximately 8%.”
By combining and comparing the results of the different sequencing methods the researchers were able to define for every measured RNA transcript, the abundance in the different cells and tissues, whether it has a polyA-tail or not (it appears that for some genes this can differ from cell type to cell type), and whether it is linear of circular. Moreover, the consortium searched and found important clues in determining the function of some of the ncRNAs. By looking at the abundancy of different RNAs in different cell types they found correlations that indicate regulatory functions, and could determine whether this regulation happens on the transcription level (by preventing or stimulating transcription of protein coding genes) or post-transcriptional (e.g., by breaking down RNAs).
All data, analyses, and results (equivalent to a few libraries of information) are available for download and interrogation in the R2 web portal, enabling the community to implement this resource as a tool for exploration of noncoding RNA biology and function.
“By combining all data in one comprehensive catalog, we have created a new valuable resource for biomedical scientists around the world studying disease processes,” said Pavel Sumazin, PhD, associate professor at the Baylor College of Medicine. “A better understanding of the complexity of the transcriptome is indeed essential to better understanding disease processes and uncovering novel genes that may serve as therapeutic targets or biomarkers. The age of RNA therapeutics is swiftly rising—we’ve all witnessed the impressive creation of RNA vaccines, and already the first medicines that target RNA are used in the clinic. I’m sure we’ll see lots more of these therapies in the next years and decades.”