In collaboration with Baylor College of Medicine and the world’s leading sequencing company, Illumina, researchers at Ghent University have built one of the most comprehensive catalogs of human transcriptomes ever created.
By intelligently combining complementary sequencing techniques, they have deepened our understanding of the function of known RNA molecules and discovered thousands of new RNAs. A better understanding of our transcriptome is essential to better understand disease processes and to discover new genes that can serve as therapeutic targets or biomarkers.
The article ‘The RNA Atlas expand the catalog of human non-coding RNAs’, published today in Nature Biotechnology, is the result of more than five years of hard work to further elucidate the complexity of the human transcriptome. Never before has such a comprehensive effort been undertaken to characterize all of the RNA molecules in human cells and tissues.
RNA of all shapes and sizes
Our transcriptome is – analogous to our genome – the sum of all the RNA molecules that are transcribed from the strands of DNA that make up our genome. However, there is no 1: 1 relationship with the latter. First, each cell and tissue has a unique transcriptome, with varying RNA production and compositions, including tissue-specific RNAs. Second, not all RNAs are transcribed from typical genes – encoding proteins – that end up producing proteins. Many of our RNA molecules aren’t used as a template to build proteins, but come from what used to be called unwanted DNA: long stretches of DNA with unknown functions.
These non-coding RNAs (ncRNAs) come in all kinds of shapes and sizes: short, long and even circular RNAs. Many of them don’t even have the tail of adenine molecules which is typical of protein-coding RNAs.
300 types of human cells and tissues and three sequencing methods
“There have been other projects to catalog our transcriptome, but the RNA-Atlas project is unique because of the sequencing methods applied,” explains Professor Pieter Mestdagh from the Center for Medical Genetics at Ghent University. “Not only did we examine the transcriptome of 300 types of human cells and tissues, but more importantly, we did so with three complementary sequencing technologies, one targeting small RNAs, the other polyadenylated (polyA) RNAs. and a technique called total RNA sequencing.
This latest sequencing technology has led to the discovery of thousands of new non-coding RNA genes, including a new class of non-polyadenylated single-exon genes and many new circular RNAs. By combining and comparing the results of the different sequencing methods, the researchers were able to define for each measured RNA transcript, the abundance in the different cells and tissues, whether or not it had a polyA tail (it seems that for some genes can differ from one type of cell to another), and whether it is linear or circular. In addition, the consortium researched and found important clues to determine the function of some of the ncRNAs. By examining the abundance of different RNAs in different cell types, they found correlations that indicate regulatory functions, and could determine whether this regulation occurs at the level of transcription (by preventing or stimulating transcription of the genes encoding for proteins) or post-transcription down RNA).
An invaluable resource for biomedical science
All data, analyzes and results (equivalent to a few libraries of information) are available for download and query on the R2 web portal, allowing the community to implement this resource as a tool for exploring biology and science. function of non-coding RNAs.
Professor Pavel Sumazin of Baylor College of Medicine: “By combining all the data into a comprehensive catalog, we have created a valuable new resource for biomedical scientists around the world studying disease processes. A better understanding of the complexity of the transcriptome is indeed essential to better understand the pathological processes and to discover new genes that can serve as therapeutic targets or biomarkers. The age of RNA therapy is rapidly increasing – we have all witnessed the impressive creation of RNA vaccines, and already the first drugs targeting RNA are in clinical use. I am sure we will see many more of these therapies in the years and decades to come. “
Reference: Lorenzi L, Chiu HS, Avila Cobos F, et al. The RNA Atlas expands the catalog of human non-coding RNAs. Nat Biotechnol. 2021: 1-13. doi: 10.1038 / s41587-021-00936-1
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