British Society for Haematology. Listening. Learning. Leading British Society for Haematology. Listening. Learning. Leading
20 April 2018

Swedish scientists have reported discovery of a new epigenetic mechanism controlling haemotopoiesis, offering potential insights into some forms of malignancy.

Dr Cristian Bellodi, of Lund University in Sweden, and colleagues studied RNA modification during the maturation of blood cells.

They say this is a "new, exciting" area of research.

They examined pseudouridination, a poorly understood epigenetic modification to RNA. Epigenetic mechanisms are central to the development of new cells from stem cells, a process that if disrupted can lead to cancer.

Tests showed that stem cells lacking an enzyme that is responsible for pseudouridination, known as PUS7, produce abnormal amounts of protein, the researchers report. This dysregulation in protein synthesis impairs stem cell growth and blocks differentiation into blood cell types.

Dr Bellodi said: "Understanding the function of RNA modifications represents a new exciting research area. We still know very little about the mechanisms by which RNA molecules are modified, and whether this affects important biological processes in our cells.

“Therefore, it is essential that we learn how specific types of chemical modifications normally regulate RNA function in our cells, in order to understand how dysregulation of this process contributes to human disease.

"Our research is potentially important for life-threatening blood cancers characterised by dysfunctional stem cells - which are common in elderly people. High protein synthesis levels could represent an Achilles' heel to eradicating cancer-initiating cells."

He adds: "Our work illustrates that this exquisite control mechanism - regulated by PUS7 and pseudouridine - is critical to adjusting the amount of proteins needed for human stem cells to grow and produce blood."


Source: Guzzi, N., Cieśla, M., Ngoc, P.C.T., Lang, S., Arora, S., Dimitriou, M., Pimková, K., Sommarin, M.N., Munita, R., Lubas, M. and Lim, Y., 2018. Pseudouridylation of tRNA-Derived Fragments Steers Translational Control in Stem Cells. Cell.

Link: http://www.cell.com/cell/fulltext/S0092-8674(18)30288-5

 

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