Knowledge about the human transcriptome assembled in comprehensive RNA-atlas

Together with Baylor College of Medicine and the world’s leading sequencing company, Illumina, researchers at Ghent University have built one of the most comprehensive catalogues of the human transcriptome ever.

By cleverly 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 uncover novel genes that may serve as therapeutic targets or biomarkers.

The article ‘The RNA Atlas expands the catalog of human non-coding RNAs’, published in Nature Biotechnology, is the result of more than five years of work to further unravel the complexity of the human transcriptome. Never before has such a comprehensive effort been undertaken to characterize all RNA-molecules in human cells and tissues.

Our transcriptome is – analogous to our genome – the sum of all RNA molecules that are transcribed from the DNA strands that make up our genome. However, there’s no 1-on-1 relationship with the latter. Firstly, each cell and tissue has a unique transcriptome, with varying RNA production and compositions, including tissue-specific RNAs. Secondly, not all RNAs are transcribed from typical – protein coding – genes that eventually produce proteins. Many of our RNA molecules are not used as a template to build proteins, but originate from what once was called junk DNA: long sequences 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 even lack the tail of adenine-molecules that is typical for proteincoding RNAs. “There have been other projects to catalogue our transcriptome but the RNA-Atlas project is unique because of the applied sequencing methods,” commented Prof. Pieter Mestdagh 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.”

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 non-coding RNA biology and function.

Prof. Pavel Sumazin of the Baylor College of Medicine, said: “By combining all data in one comprehensive catalogue, we have created a new valuable 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 disease processes and uncover 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.”

View the R2 RNA Atlas: https://hgserver1.amc.nl

Reference

Lucia Lorenzi, Hua-Sheng Chiu et al.
The RNA Atlas expands the catalog of human
non-coding RNAs. Nature Biotechnology. 2021.

https://doi.org/10.1038/s41587-021-00936-1