Tandem repeats: useful for survival,but not easy to work with

18 March 2018
​Researchers from the lab of Kevin Verstrepen tell us more about their recent study

Although protein degradation receives much less attention than protein synthesis, breaking down damaged, unnecessary and harmful proteins is just as important as generating new ones. In fact, changes in protein degradation and protein half-lives can cause neurodegeneration and cancer. A key degradation system depends on the addition of a ‘ubiquitin tag’ to proteins that need to be degraded. Interestingly, the eukaryotic stressinduced polyubiquitin gene UBI4 is composed of tandem repeats, with each repeat encoding a ubiquitin moiety.

Rita Gemayel and her colleagues in the Kevin Verstrepen lab (VIB–KU Leuven Center for Microbiology)
show that the number of ubiquitin units encoded by the UBI4 gene differs greatly between different species, and even within a species, including different yeast strains as well as humans.

Did your study uncover any surprising new insights into UBI4 tandem repeats?
Kevin: “Tandem repeats have been a longstanding topic in the lab. When we screened the yeast genome to find all repeats located within coding regions, we were surprised to find that the UBI4 gene did not just contain a repeat, but instead solely consists of one big tandem repeat! We found that the unusual structure of the UBI4 gene allows yeast cells to quickly produce more copies of ubiquitin and rapidly respond to sudden
environmental stress.

“Even more, the number of ubiquitin repeats that is optimal for stress survival differs between stress conditions, indicating that natural variation in repeat units may optimize the chance for survival. Natural instability in the number of ubiquitin repeats encoded by UBI4 may also serve as an elegant alternative to copy number variation, enabling cells to rapidly tune the ubiquitin production rate in times of stress.”

Did you run into any challenges during the project?
Rita: “Because of their intrinsic instability and the problems with sequencing and amplification, working with tandem repeats gave me a lot of headaches. But after a while, I learned how to make things work. Perhaps we should publish a paper on how to live with difficult repeats”.

Publication
Gemayel et al., Nat.Comm. 2017


Go back to the overview on 'Microbiology'


©VIB-Ine Dehandschutter