New research aids understanding of how genes are regulated

22 August 2017

A decrease in expression of certain genes within the cells of the body has been implicated in cancer, cardiovascular disease, autoimmune disease and neurological disorders. One way genes can be inhibited is through the action of microRNAs, small non-coding molecules of ribonucleic acid (RNA). To help researchers understand more about the role of microRNAs in disease, an international consortium of scientists has produced an interactive map that displays where these molecules are expressed and how they might work within the body.

The findings, published in Nature Biotechnology, are the latest work of the FANTOM5 consortium. Led by Dr Michiel de Hoon from RIKEN, Japan, and Professor Alistair Forrest from the Harry Perkins Institute of Medical Research. Australian researchers included Professor Christine Wells and Mr Cheng-Ta Edward Huang at the University of Melbourne’s Centre for Stem Cell Systems, A/Professor Timo Lassmann at the Telethon Kids Institute and Professor Peter Klinken and Dr Louise Winteringham at the Harry Perkins Institute of Medical Research.

The team mapped, at unprecedented scale, the levels of thousands of microRNAs in hundreds of human cell types. This information was developed into a free online map that allows anyone to explore the patterns of microRNAs across tissues of the body. For example, University of Melbourne researchers contributed information about microRNAs that are active in immune cells responding to an infection, and showed that these are also more likely to be involved in autoimmune diseases.

This publication completes the FANTOM5 transcriptome catalogue commenced in 2009 by adding microRNAs to their previously published expression atlases. Together these provide an exhaustive survey of the components required to fine-tune the behaviour of genes during healthy development, aging and disease. The resources of the microRNA atlas are available here.

Professor Forrest plans to apply the systematic approaches used in the FANTOM5 project to the recently Cancer Research Trust funded Single cell cancer initiative. “We have found that the systematic approach used in the FANTOM projects is incredibly powerful.” Said Prof Forrest, “By systematically studying hundreds of samples from different tissues and cancers we can standardise the analyses and will be able to compare and contrast across patients and tumour types.” 

Commenting on the work, Professor Christine Wells said, “MicroRNAs form part of a broad genetic lexicon that help us understand how DNA controls the identity and function of cells. This study is important, not only because it is such a comprehensive map, but also because it helps build the rules that let us identify microRNAs. This sets the groundwork to help researchers add to the microRNA atlas as new tissues or disease states are surveyed.”

Professor Wells is also the Deputy Program Leader for Stem Cells Australia initiative, an Australian Research Council-funded Special Research Initiative in Stem Cell Science. 

FANTOM5 received the Scopus Eureka Prize for Excellence in International Scientific Collaboration Prize at the 2016 Australian Museum Eureka awards.

For more information

De Rie D. et al. An integrated expression atlas of miRNAs and their promoters in human and mouse. Nature Biotechnology (2017)