Developmental Biology - Gene Transcription|
Insight Into How Genes Work
Scientists combine two, thirthy year old theories into 'one concrete idea'...
Pioneering research at the University of Exeter's Living Systems Institute in the United Kingdom, has a fresh insight into one of the pivotal building blocks of life - how gene information is translated. Thanks to a team led by Dr Steven West, scientists better understand how genes are read.
The human genome - which is your entire set of DNA - is made up of thousands of genes. Each unit of information on a DNA strand is copied into a messenger molecule, called RNA, in a process known as 'transcription'.
During transcription, a molecule in the cell called RNA polymerase attaches to a DNA strand at its beginning, and copies information in that gene to an RNA molecule, before terminating the transcription process at the end of that gene.
Crucially, in order for this process to be carried out safely in the organism carrying that gene, it's vital to start and stop in the correct place - or else the RNA transcript of the gene message may make no sense, or even be harmful.
Now, new research, published in Genes & Development, has given us fresh insight into how the transcription process terminates.
Traditionally, there were two models thought to explain transcription:
(1) the allosteric model which suggests properties of RNA polymerase are changed at the ends of genes causing transcription to stop; and
(2) the torpedo model that suggests that at the ends of genes, a molecular torpedo jumps onto the RNA - gives chase to RNA polymerase and upon reaching it - knocks it off the DNA strand.
These two models have been debated for over thirty years attempting to understand this elusive final step in transcribing information from DNA. The new research, however, suggests a combination of the two is more likely to explain the process.
New research shows that:
• The allosteric mechanism slows down RNA polymerase.
• Once slowed, it is a much easier target for the molecular torpedo.
"Many people will be aware of the therapeutic potential of gene editing technology. However, it is also extremely useful as a biological tool to probe cellular processes as we have done.
When we used gene-editing to remove the molecular torpedo, we were excited to see that the RNA polymerase took much longer to stop - and that this problem was evident on most genes."
Steven West PhD, Senior Lecturer, Molecular Microbiology and Biotechnology, University of Exeter, United Kingdom.
The allosteric and torpedo models have been used for 30 yr to explain how transcription terminates on protein-coding genes. The former invokes termination via conformational changes in the transcription complex and the latter proposes that degradation of the downstream product of poly(A) signal (PAS) processing is important. Here, we describe a single mechanism incorporating features of both models. We show that termination is completely abolished by rapid elimination of CPSF73, which causes very extensive transcriptional readthrough genome-wide. This is because CPSF73 functions upstream of modifications to the elongation complex and provides an entry site for the XRN2 torpedo. Rapid depletion of XRN2 enriches these events that we show are underpinned by protein phosphatase 1 (PP1) activity, the inhibition of which extends readthrough in the absence of XRN2. Our results suggest a combined allosteric/torpedo mechanism, in which PP1-dependent slowing down of polymerases over termination regions facilitates their pursuit/capture by XRN2 following PAS processing.
Joshua D. Eaton, Laura Francis, Lee Davidson and Steven West.
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Current gene transcription model for protein formation. CREDIT Wikipedia