Work on gene-silencing machinery could help fight viral, other diseases
Released on 12/21/2006, at 1:00 PM
Office of University Communications
University of Nebraska–Lincoln
Newly published research from the University of Nebraska-Lincoln Plant Science Initiative expands understanding of RNA interference -- a process that silences genes and holds promise in combating disease.
A research team led by biologist Heriberto Cerutti identified a novel gene in the single-cell green alga, Chlamydomonas reinhardtii, that is required for RNA interference. The research builds on Cerutti's earlier work on transgene and transposon silencing and was published in the Dec. 22 issue of the international journal Science.
In 2000, Cerutti's team published results of earlier research in Science. Both papers provided insights into regulatory mechanisms that could control or "silence" genes.
"RNA interference (RNAi) is an important area of research and what we're trying to do is explain how this mechanism works in controlling the expression of endogenous genes (the organism's genes) as well as in the prevention of viral infections," said Cerutti, an associate professor in the School of Biological Sciences and in the Center for Biotechnology.
"A better understanding of how cells express their genes and cope with viral infections will have important biotechnological implications, particularly for genetic engineering in animal, plants or fungi," he said. "This is also relevant to human diseases, and RNAi will someday be used to combat or prevent diseases."
Cerutti said the instructions contained in genetic material are translated through an intermediary molecule, RNA, into proteins, which are the building blocks of all cells and organisms. Viruses also use RNA to take over the cellular machinery and multiply. RNA interference is a mechanism for the RNA-guided regulation of gene expression, and involves the sequence-specific degradation of RNA molecules, preventing protein production or viral replication.
The phenomenon of RNA interference was discovered in 1998 and could help fight diseases resulting from viral infection or from the production of defective proteins such as Huntington's disease. American scientists Andrew Fire and Craig C. Mello shared the Nobel Prize in Physiology or Medicine in 2006 for their discovery of RNAi.
Cerutti's team uses the single-celled alga as a model system to study the molecular machinery responsible for gene silencing. The team can introduce foreign genes, called transgenes, into cells, characterize how they are repressed, and isolate genes affecting this process. Some of the newly identified genes also appear to be involved regulating endogenous gene expression and in antiviral responses.
"The technology has already started being used, but there are still questions about how the machinery behind it works. Our work involves trying to fill these holes, identifying the molecular components of RNAi and explaining how the machinery actually works."
Cerutti said the major hurdles in utilizing RNAi gene silencing include figuring out how to deliver RNAi drugs to the right targets and how to avoid veering off-target and shutting down good genes or cellular processes. He said his team and others will continue to focus on these hurdles.
Co-authors of the Science paper are graduate students Fadia Ibrahim and Jennifer Rohr, postdoctoral researcher Won-Joong Jeong and undergraduate student Jennifer Hesson.
The National Science Foundation and the National Institutes of Health fund this research.
CONTACT: Heriberto Cerutti, Assoc. Professor, Biological Sciences, (402) 472-0247