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Twice the splice of life

Published on 17 January 2023

New work from the University of Dundee reveals a basic feature of how our genomes are organized, and our genes are processed. This work has been published in the journal eLife.

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L-R Prof. Geoff Barton, Prof. Gordon Simpson, Dr Matthew Parker Dr Nisha Joy

Our genes are coded in segments of DNA in chromosomes. When genes are switched on, they are first copied into RNA, which provides the recipe for the proteins made in our cells. The different segments of our genes in RNA are cut and joined together in a process called splicing. The ends of the RNA segments are defined by features called splice sites and are identified by a molecular machine in our cells called the spliceosome. Researchers in Dundee have now found that splice sites can be classified into two major types and that this is true of human genes and many other species.

Professor Gordon Simpson, co-corresponding author from the Division of Plant Sciences in the School of Life Sciences at Dundee said, “We studied how plants used splicing to modulate genes which control flowering. We found an enzyme that chemically modifies a small RNA called U6, which functions as part of the spliceosome, was important for splicing accuracy. We found that different splice sites would be used without the chemical modification of U6. This allowed us to classify splice sites into types that were strongly dependent upon the chemical modification of U6 and sites that were not. When we applied this classification to different genome sequences we could find these two types of splice site in many other species too – including humans.”

This research provides a new basic insight into how our genes and genomes are organized. It will help to inform us whether inherited genetic changes in splice sites might lead to disease or how drugs that modulate splicing can be designed. Since complex splicing choices of RNA segments are found in many species, this research also tells us how splicing can be made either simpler or more complex during evolution.

This collaborative project involved researchers from the Universities of Dundee, Leeds and Oxford. It was supported by funding from Biotechnology and Biological Sciences Research Council, HORIZON EUROPE Marie Sklodowska-Curie Actions, University of Dundee Global Challenges Research Fund and Wellcome Trust.

Read the paper on the eLife website.

Story category Research