How the genome keeps out unwanted intruders

How the genome keeps out unwanted intruders

Scientists are a step closer to understanding the information in our genome thanks to pioneering research carried out at the Babraham Institute.  In a paper published today, scientists at the BBSRC supported research institute provide insights into how the genome may defend itself from unwanted intruders.

The human genome is very large but only 1% of it consists of genes. Genes account for visible characteristics such as hair or eye colour, our height, or our susceptibility to develop certain diseases. Much of the remaining vast 99% of the genome is often considered ‘junk DNA’, but surprisingly this junk DNA has been found to produce copious amounts of a molecule called RNA which is normally associated with genes.

When RNA is made from junk DNA it is often called non-coding RNA (as opposed to that made by genes which is called coding RNA because it contains meaningful messages for the cell). Now scientists working in a Wellcome Trust-funded laboratory at the Babraham Institute have shown that this non-coding RNA has an important function, allowing cells to distinguish unique sequences from those present many times in the genome.

Why do cells need to do this? Much of the junk DNA in the genome is made up of genetic parasites called transposable elements. They often first emerge from the outside world as a type of virus which inserts itself into the genome. Afterwards, the parasitic DNA can get amplified many times and can eventually interfere with the normal function of the genome.

An ancient defence mechanism called RNA interference (RNAi) can recognise and silence such transposable elements, but needs to distinguish them from the rest of the genome. The new results show that RNA interference can use non-coding RNAs to identify sequences with many copies in the genome. This allows RNA interference to recognise transposable elements as they spread through the genome. This only works if the whole genome is turned into RNA otherwise these transposable elements could remain hidden. This means that non-coding RNAs produced throughout the genome act as a defence mechanism that allows the cell to detect invading parasites before they cause too much damage.

Dr Jon Houseley, who directed the work, said, “This work reveals the function of some of the more mysterious products of the genome, and helps us understand the consequences of genome alterations. For example, some normal genes can be amplified in cancer cells with dangerous consequences; our data reveals the existence of a mechanism by which cells can protect themselves against such changes.”

Dr Michael Dunn, Head of Genetics and Molecular Sciences at the Wellcome Trust said: “Findings like these help us to understand the basis of our genome. Understanding the body’s defense mechanisms at the molecular level can help inform development of new treatments and guide future research”.

Director of the Babraham Institute, Professor Michael Wakelam, adds “Jon Houseley’s group have not only provided a function for ill-defined regions of the genome, but have defined an essential integral self defence mechanism which has significant future potential to define novel therapeutic targets for a range of diseases, including cancer.  In addition, this work addresses changes that can occur during the ageing process. This work clearly demonstrates the outstanding opportunities presented through continuing support for basic bioscience research as carried out at the Babraham Institute.”

This paper is published in ELife. More information about Jon Houseley's research and other publications can be found at: www.babraham.ac.uk/our-research/epigenetics/jon-houseley

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About the Babraham Institute:
The Babraham Institute undertakes world-class life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Our research focuses on cellular signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing. The Institute is strategically funded by the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation, through an Institute Core Capability Grant and also receives funding from other UK research councils, charitable foundations, the EU and medical charities.
 
Website: www.babraham.ac.uk
 
The Biotechnology and Biological Sciences Research Council (BBSRC) is the UK funding agency for research in the life sciences. Sponsored by Government, BBSRC annually invests around £450 million in a wide range of research that makes a significant contribution to the quality of life for UK citizens and supports a number of important industrial stakeholders including the agriculture, food, chemical, health and well-being and pharmaceutical sectors. BBSRC carries out its mission by funding internationally competitive research, providing training in the biosciences, fostering opportunities for knowledge transfer and innovation and promoting interaction with the public and other stakeholders on issues of scientific interest in universities, centres and institutes.
 
Website: bbsrc.ukri.org/