A body-wide map of gene switches active in different cells

A microrna molecule.
A microRNA molecule.
Credit: Molekuul / Getty

Every cell in the body operates off the same genetic instruction manual – our genome. Yet a liver cell bears scant resemblance to a nerve cell or a bacteria-gobbling white blood cell. That’s because for each cell, only a specific subset of instructions, or genes, is required.

Now, an international consortium of researchers, led by a team at the RIKEN Center for Life Science Technologies in Japan, has created a body-wide map of some of the molecular switches operating in different cells that ensure only the right genes are turned on.

The switches, called microRNAs (miRNAs), are small snippets of RNA, a molecule similar to the DNA that comprises the 3 billion letters of the human genome. miRNAs hunt down and mark for destruction read-outs of genes that are en route to being decoded into proteins, molecules which, as enzymes, hormones and structural scaffolds, are the workhorses of a cell.

miRNAs play critical roles in essential biological processes, from maintaining immune health to kicking off labour. If miRNAs are out of whack, diseases like cancer can result.

The team sifted through close to 500 libraries of short RNAs sequenced from human and mouse cell extracts. Dozens of different human cell types – 121 in total – were included in the mix. The researchers were then able to identify which miRNAs were present in each cell type.

For more than 1300 human and 800 mouse miRNAs, the researchers also identified what are effectively the ‘switches for the switches’ – the sequences in the genome that govern when the miRNAs are themselves turned on.

Instructions for miRNAs are nestled in among the vast stretches of DNA that surround the 20,000-odd protein-coding genes in our genome. These regions have been disparagingly referred to as “junk DNA”, but projects that have turned up blueprints for regulatory sequences like miRNAs show that they are anything but wastelands.

The atlas, which is available online, will be invaluable to researchers around the globe trying to understand the ebbs and flows of gene activity that govern development and prevent disease.

“We believe it will be an essential resource for understanding microRNA regulation and its role in human disease,” says Michiel de Hoon of the RIKEN Center for Life Science Technologies.

The work is published in Nature Biotechnology.

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