A group of researchers from Japan and Australia have completed a landmark study where they revealed that long non-coding RNAs, a poorly understood and highly controversial class of genes, may link with major diseases, including inflammation and cancer.
The group generated a comprehensive atlas of 27,919 long non-coding RNAs and summarised their expression patterns across the major human cell types and tissues – the first time this has been achieved.
By combining this atlas with genomic and genetic data, their results suggest that two-thirds 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.
The findings, published in the journal Nature, were the latest work of the FANTOM5 consortium led by West Australian researcher Professor Alistair Forrest who is based at the Harry Perkins Institute of Medical Research and the University of Western Australia. Professor Christine Wells at the University of Melbourne and Deputy Program Leader of the Stem Cells Australia initiative, Dr Alison Testa at the Harry Perkins Institute of Medical Research, together with A/Professor Timo Lassmann and Dr Dave Tang from the Telethon Kids Institute were the other Australian researchers involved in this project. Australian researchers worked closely with colleagues at RIKEN Japan.
Commenting on their findings Professor Forrest said, “By integrating the improved gene models with data from gene expression, evolutionary conservation and genetic studies, we find compelling evidence that the majority of these long non-coding RNAs appear to be functional, and for nearly 2,000 of them we reveal their potential involvement in many genetic traits including predisposition to heart disease, obesity, depression, autoimmunity and various cancers.”
Professor Wells added, “It is notoriously difficult to predict the function of these long non-coding RNAs, because they lack the protein features that we are most familiar with. This study is significant because it uses genetics and ‘chromosome geography’ to infer function. The study suggests that noncoding RNAs regulate the flow of genetic information in different tissues, and disruption of these molecules occurs in many different types of disease."
This publication is another important milestone for the FANTOM consortium, which in 2014 and 2015 used CAGE technology to build atlases of the promoters and enhancers in our genomes.
The importance of the achievements of FANTOM5 consortium was acknowledged by the 2016 Eureka Scopus prize for Excellence in International Scientific Collaboration.
For more information:
Hon C-C et al (2017) Nature An Atlas of Human Long Non-Coding RNAs with Accurate 5′ Ends. doi:10.1038/nature21374
The resources of the long non-coding RNA atlas are available here.
FANTOM CAT Browser - an web application allows users to browse genes, view their genomic loci through ZENBU, filter by their annotations, intersect them with their associated sample ontologies or traits, and download the relevant data.
Ground-breaking new study doubles the estimate of our functional genes
. Perkins Institute of Medical Research.
Comprehensive Atlas of Long Noncoding RNAs Yields Surprising New Role Genetic Engineering & Biotechnology News (2 March, 2017).