THE STRUCTURE of a protein complex crucial for gene expression has been revealed, showing how viruses such as influenza target the protein within the cell, disrupting gene expression. This is according to researchers from the Medical Research Council (MRC) and the University of Oxford, Oxford, UK, who utilised the cryo-electron microscopy technique to make their findings.
Fully understanding the mechanisms of the cleavage and polyadenylation factor (CPF) protein has previously proven difficult, which has now been made possible by cryo-electron microscopy. “Understanding the structure and function of intact CPF, and how it is assembled, has been a central question in the field of gene expression for decades; it is such a fundamental protein but we still do not understand how it works. This was a huge technical challenge because very few structures have been built entirely from scratch using cryo-electron microscopy data. We were very excited to finally build the first atomic model of the structure of part of CPF,” explained senior author Dr Lori Passmore, Group Leader, MRC Laboratory of Molecular Biology.
The CPF is a complex enzyme that plays a crucial role in the process of gene expression, adding a ‘poly-A tail’, a long string of adenosine molecules, to the end of each new mRNA. The mRNA travel from the nucleus to the cytoplasm, where its instructions are used to assemble a protein. The tail is needed for the mRNA to be transported out of the nucleus, and the length of it determines the amount of time the mRNA is present in the cell and how often it translates into a protein.
In the study, it was discovered that a protein from the influenza virus was able to block CPF from interacting with mRNA by binding, and halt gene expression in the cell. These findings has provided a basis for further research to understand the role of CPF in other diseases.
“Now, having the structure of CPF will enable future research into how this important protein works in normal cells, but it also opens up opportunities to understand its role in viral infections and diseases such as cancer,” commented Dr Passmore.
James Coker, Senior Editorial Assistant