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Test-tube breakthrough holds promise for cancer, heart disease research

Researchers at 捆绑SM社区 have successfully used a class of tiny nucleic acids called microRNAs to control messenger RNA, one of the major gene regulators in life, outside the confines of a living cell for the first time.

In research led by 捆绑SM社区 postdoctoral fellows Geraldine Mathonnet and Marc Fabian, Dr. Nahum Sonenberg, James 捆绑SM社区 Professor of Biochemistry, Dr. Thomas Duchaine, assistant professor in biochemistry at the 捆绑SM社区 Cancer Centre, and several colleagues have discovered the biological process by which small gene-controlling molecules, microRNAs, inhibit the expression of messenger RNA in mammals. Their findings were published Thursday, July 26, in the journal Science. Messenger RNA acts as a living cell鈥檚 duplicating mechanism, copying the blueprint to construct new proteins from DNA. Though previous researchers have successfully inhibited messenger RNA with microRNAs in other biological systems such as flies, doing so in the test tube with mammalian systems has been a longstanding goal.

鈥淯ntil now, all the research on microRNAs was done in the cell,鈥� explains Sonenberg. 鈥淏ut in the cell, the investigator has limited abilities to control the reaction, which caused considerable controversy on how microRNAs control gene expression. Working in a test tube, you can add and remove whatever you want and you are in control of the process. That鈥檚 what was missing, and that鈥檚 what we have created now.鈥�

Ribonucleic acid, or RNA, is a single-stranded nucleic acid similar to the familiar double-stranded DNA, or deoxyribonucleic acid. DNA contains within it the genetic code for the construction of proteins from amino acids, but it is RNA, and more specifically the messenger RNA (mRNA), that actually does the heavy lifting. Like a biological photocopy machine, RNA transcribes the amino acid assembly instructions from the DNA and transports them to the appropriate place in the cell where the proteins are generated, a process known as translation. While mRNAs encode genetic information, microRNAs control its flow. MicroRNAs are a class of small RNA molecules that pair to mRNAs and control their expression, but exactly how this happens remained unclear until now.

鈥淭here are about 25,000 genes in the human genome, and a third of them are regulated by microRNA,鈥� says Sonenberg. 鈥淭his means a lot and it has relevance to many diseases, especially cancer. MicroRNAs are important for cancer progression, in cardiac disease, in pancreatic disease, and many others. They control the genes that are important for our very survival.鈥�

Other researchers contributing to this study are based at the University of Eastern Piedmont, Case Western Reserve University, Warsaw University and the Friedrich Miescher Institute for Biomedical Research in Basel, Switzerland.

Please note: The full report will be available online in advance of print at as of Thursday, July 26, at 2:00 p.m. EDT.