Polyglutamine Repeats Play Key Role in Normal Functional Development; Often Found in Proteins With Regulatory Functions; Act As Tuning Dial; Repeat Number Modulates Transcriptional Responses of Genes; Too Many Repeats Can Cause Diseases Like Huntington’s

Scientists at VIB (Flanders Interuniversity Institute for Biotechnology) and KU Leuven (Katholieke Universiteit Leuven) in Belgium have discovered that variable repeats in the triplet nucleotide code (CAG) for the amino acid glutamine tune the function of the protein in which the resulting polyglutamine residues (e.g., the huntingtin protein of Huntington’s disease). To date, these repeats were known only to cause severe neurodegenerative diseases such as Huntington’s. The new findings from Belgium show that polyglutamine repeats may be more than just harmful elements. The study was published online on August 6, 2015 in an open-access article in Molecular Cell and opens the door to further studies exploring new therapies for human polyglutamine repeat diseases. Moreover, this study lays the foundation for future research into the role of repeats in the emergence and evolution of novel functions and life forms. The Molecular Cell article is titled “Variable Glutamine-Rich Repeats Modulate Transcription Factor Activity.” Excessive numbers of glutamine-rich repeats in various human proteins are known to result in severe neurodegenerative disorders such as Huntington’s disease. Little is known, however, about the physiological role of these repeats and the consequences of more moderate repeat expansions. Dr. Rita Gemayel (VIB/KU Leuven) said, “We found that the polyglutamine repeats act like the dial on a tuner. The length of the repeat modulates the transcriptional response of genes in the cell. More specifically, using a polyglutamine-containing protein called Ssn6 as a model, we showed that the repeat length modulates the solubility of Ssn6 and its interaction with other proteins.
Login Or Register To Read Full Story