How does the MYCN protein change the way genetic information is read in poor prognosis childhood cancer?

Cancer cells grow out of control, which is due to changes in their DNA, the set of genetic instructions that every cell contains. These instructions tell a cell how to behave and how to make essential proteins, so when there are changes it can cause serious issues that lead the cell to become cancerous.

One thing that can change is which genes, which code for specific essential proteins, are turned on or off.  Switching on a gene copies that gene’s DNA information into another type of genetic molecule - messenger RNA molecules. This is called DNA transcription. After this process, the messenger RNA is finally translated into the specific protein that the gene coded for.

The reading of genetic code on the messenger RNA, and conversion into protein is known as translation. The key molecules for this process are called transfer RNAs (tRNAs). Changes in the amount genes are transcribed or translated (through tRNAs) can result in altered levels of proteins in the cell, such as growth-promoting or growth-inhibiting proteins. Maintaining the correct balance of these proteins is vital to make sure a cell grows in the correct way.

In many childhood cancers, including Wilms tumour, neuroblastoma, rhabdomyosarcoma and medulloblastoma, there is too much of a growth-promoting protein called MYCN. This protein leads to huge changes in the amount of other proteins in the cell, which it does by altering the transcription of other genes. There is a lot of research on MYCN’s control of gene transcription, including LPT-funded work by Professor Karim Malik at the University of Bristol. His work found that, in Wilms tumour, MYCN interacts with a group of genes to affect translation in proteins, as well as DNA transcription.

In this project, Professor Malik wants to find out how MYCN alters the translation of genetic code into proteins. He believes that the MYCN protein is able to modify the structure of tRNAs. This is likely very important in cancer development, but this ability of MYCN and how it works have not been studied before. Professor Malik believes that this work assessing how MYCN alters the composition of tRNAs, and therefore translation, will pave the way for new diagnostic, prognostic and treatment methods for the many childhood cancers that involve MYCN.