Pioneering research gives fresh insight into one of pivotal building blocks of life

Insight into how genomic information is read

The quest to better understand how genomic information is read has taken a new step forward, thanks to pioneering new research.

A team of scientists, led by Dr Steven West at the University of Exeter’s Living Systems Institute, have revealed a fresh insight into how genes are copied.

The human genome – or the entire set of DNA – comprises of thousands of genes. These units of information are copied into a messenger molecule, called RNA, by a complicated process known as ‘transcription’.

For the process, a factory molecule called RNA polymerase attaches to DNA at the beginning of a gene, copies the information in the gene into an RNA molecule, before finally terminating the transcription process at the end of a gene.

Crucially, in order for this process to be carried out safely to the host organism, it is vital to start and stop in the correct place or else the message – in this case the RNA transcript – may make no sense or even cause harm.

The new research, published in Genes & Development, has given a fresh insight into how the transcription process stops – or is terminated.

Traditionally, there have been two models that are thought to explain this – the allosteric model that suggests that the properties of RNA polymerase are changed at the ends of genes to cause it to stop; and the torpedo model that suggests that, at the ends of genes, a molecular torpedo jumps onto the RNA and gives chase to the RNA polymerase bumping it off the DNA when it catches it.

These two models have been debated now for over thirty years in a bid to understand this elusive final step in the transcription cycle. The new research, however, suggests a combination of the two processes is actually more likely to explain the phenomenon. The research shows that the allosteric component of the mechanism applies a brake that slows down the RNA polymerase, which can be thought of as a juggernaut. Once slowed, it represents a much easier target for the molecular torpedo.

Dr West explained – “for many years these two models were pitted against one another. The fact that they work together is satisfying and explains why evidence had built up to support both. This will help us to better understand the transcription cycle, and how cells use their genetic information correctly”.

A unified allosteric / torpedo mechanism for transcriptional termination on human protein-coding genes is published in the journal Genes & Development.

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