A Research Blog

Assistant Professor Owen Rackham from the Duke-NUS Centre for Computational BiologyAssistant Professor Owen Rackham, from the Centre for Computational Biology at Duke-NUS Medical School, shares more about a study he co-authored on long non-coding RNAs.

In recent years a great deal of attention has been focused on understanding the parts of our genome that don’t encode for proteins. A landmark study has mapped out these poorly understood and highly controversial class of genes, known as long non-coding RNAs and in doing so has found evidence of evolutionary selection and links with major diseases, including cancer.

This is the latest work from the FANTOM5 consortium, an international group of researchers whose aim is to annotate and understand the genome led by RIKEN - Japan's largest research institute for basic and applied research. I am a member of FANTOM5 and coauthor of the findings that were published in Nature last month.

The work involved generating a comprehensive atlas of 27,919 long non-coding RNAs and summarised, for the first time, their expression patterns across the major human cell types and tissues.

By intersecting this atlas with genomic and genetic data, their 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.

This work will help to address the controversy that surrounds the functional potential of these long non-coding RNAs. Furthermore, the integration of multiple other data sources including gene expression, evolutionary conservation and genetic association to disease has revealed already that nearly 2000 of these genes can be linked to diseases such as heart disease, obesity and various cancers. The effect doubling the size of our catalogue of genes will only make future detection of such associations easier, and as such is an invaluable contribution to the field.

This recent publication is another landmark discovery facilitated by the FANTOM consortium, and it demonstrates the power in successful international collaboration between both wet and dry scientists.

Asst Prof Rackham is an active member of the FANTOM5 consortium. He has contributed to the two main papers which describe the human promoterome [2] and enhancerome [3] as well having used the data to predict the transcription factors required to reprogram between any two human cell types [mogrify, 4] as well as describing the evolution of protein coding genes [5].

References:

1.       Hon C. et al. FANTOM5 atlas of human long non-coding RNAs. Nature (2017) http://dx.doi.org/10.1038/nature21374

2.       Forrest A. et al. A promoter level mammalian expression atlas. Nature (2014) http://dx.doi.org/10.1038/nature13182

3.       Andersson, R. et al. An atlas of active enhancers across human cell types and tissues. Nature (2014) http://dx.doi.org/10.1038/nature12787

4.       Rackham et al. A predictive computational framework for direct reprogramming between human cell types. Nature Genetics, 2016 http://dx.doi.org/10.1038/ng.3487

5.       Sardar et al. The Evolution of Human Cells in Terms of Protein Innovation, MBE (2015), https://doi.org/10.1093/molbev/mst139

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