An integrated map of microRNAs and their promoters

Tuesday 22 August 2017

MicroRNAs, short RNA molecules that inhibit gene expression have been implicated in cancer, cardiovascular disease, autoimmune disease and neurological disorders. Knowing which cell types they are expressed in and how they are regulated is key to uncovering their role in disease.

Alistair ForrestThe findings, published in Nature Biotechnology today, are the latest work of the FANTOM5 consortium, an international group of researchers centred at RIKEN Japan and was led by Perkins researcher Professor Alistair Forrest and Yokohama based researcher Dr Michiel de Hoon.

The team measured the levels of thousands of microRNAs and mapped the genomic regions that turn them on (promoters), across hundreds of human cell types using next generation sequencing (Cap Analysis of Gene Expression and short RNA-seq).

This data has been combined into a free online database that will allow researchers anywhere in the world to see where their favourite microRNA is expressed, or see what are the most specific microRNAs expressed in the cell or tissue type they study. For example microRNAs that are active in different immune cells are more likely to be involved in autoimmunity than those expressed in neurons.

Other Australian based authors in today’s publication are Professor Peter Klinken and Dr Louise Winteringham at the Harry Perkins Institute of Medical Research; Associate Professor Timo Lassmann at the Telethon Kids Institute and Professor Christine Wells at the University of Melbourne.

Today’s publication completes the FANTOM5 transcriptome catalogue commenced in 2009 by adding microRNAs to their previously published expression atlases of human promoters, enhancers and long non-coding RNAs published in 2014-17 [refs 2-5]. The resources of the microRNA atlas are available at http://fantom.gsc.riken.jp/5/suppl/De_Rie_et_al_2017/ .

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 Professor 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”.


References:

  1. De Rie D. et al. An integrated expression atlas of miRNAs and their promoters in human and mouse. Nature Biotechnology (2017) http://dx.doi.org/10.1038/nbt.3947
  2. Hon C. et al. FANTOM5 atlas of human long non-coding RNAs. Nature (2017) http://dx.doi.org/10.1038/nature21374
  3. Forrest A. et al. A promoter level mammalian expression atlas. Nature (2014) http://dx.doi.org/10.1038/nature13182
  4. Andersson, R. et al. An atlas of active enhancers across human cell types and tissues. Nature (2014) http://dx.doi.org/10.1038/nature12787
  5. Arner E. et al. Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells. Science (2015) http://dx.doi.org/10.1126/science.1259418
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