Certain RNA molecules, ‘photocopies’ of DNA which previously had no known function, have been shown to regulate chromosomal DNA replication and may play a role in the development of cancer, an innovative study published in September’s Molecular and Cellular Biology* reveals.
A team of Cancer Research UK funded scientists at the University of Cambridge have, for the first time, shown that a specific class of RNA molecules, called Y RNAs, are essential factors in the process of DNA replication in human cells. Until now, Y RNAs had been considered ‘junk’ RNA, because no significant direct function had been discovered.
DNA replication is a process that occurs naturally in the body, enabling cells to divide and multiply. When something goes wrong with the regulation of this process, cells can replicate uncontrollably, a major characteristic of cancer. These Y RNA findings could prove important in increasing our understanding of cancer and may lead to new ways of diagnosing and treating the disease in the future.
Y RNAs belong to a larger collection of so-called non-coding RNAs, many of which have roles in the regulation of key cellular processes. However, this is the first time a function for Y RNAs has been identified. Dr Torsten Krude, lead researcher on this project at the University of Cambridge, says: “The control of DNA replication is a fundamental step in the cell cycle and its understanding may provide vital new leads in the search for new treatments for cancer.
“Surprisingly, despite decades of intense research around the world, the full list of molecules involved in DNA replication remains incomplete. The existence of Y RNAs has been known since the 1980s, but no function has previously been described for these molecules.
“We are very excited by the next stage of our research, when we will attempt to determine which cellular proteins interact with Y RNAs to regulate DNA replication”.
The researchers looked specifically at four human Y RNA molecules in their search for factors that are essential for DNA replication in human cells. In addition to these Y RNAs, DNA replication also requires other well-known protein factors.
However, Y RNAs were crucial for DNA replication and the total level of Y RNAs present in a sample influenced the extent of DNA replication. Once the researchers had shown the importance of Y RNAs in DNA replication in a test tube, they went on to show that these molecules were also important for DNA replication in human cells, and therefore for cell multiplication.
Because cancer cells multiply inappropriately, and often more frequently than healthy cells, it is possible that they will contain higher levels of Y RNAs. If so, this could lead to new additional ways of diagnosing cancer in the future. Furthermore, due to their importance in DNA replication – a process that is key to the development and progression of cancer – Y RNAs may have potential as anti-cancer drug targets.
Professor John Toy, Cancer Research UK’s Medical Director said: “Although this research is at an early basic stage, it’s exciting work. It is crucial that we enhance our understanding of the DNA replication process, as it will help scientists figure out exactly how cancer cells behave. This in turn will help Cancer Research UK to achieve its objectives of improving the diagnosis and treatment of cancer.”
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* Functional requirement of non-coding Y RNAs for human chromosomal DNA replication. Christov, C., Gardiner, T.J., & Krude, T. Molecular and Cellular Biology. Volume 28, Issue 18, p6993-7004.
DNA stands for DeoxyriboNucleic Acid. A cell’s DNA is found in its nucleus, and carries the genetic information necessary for the cell’s organisation and functioning.
RNA is a nucleic acid found in all living cells. It plays a role in transferring information from DNA to the protein-forming system of the cell.
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