Grants support RNA research

1:41 p.m., April 6, 2005--University of Delaware researchers have received two grants totaling $585,000 for research in the new field of small ribonucleic acid (RNA) molecule profiling.

The work is supported by grants of $200,000 from the National Science Foundation (NSF) and $385,000 from the U.S. Department of Agriculture (USDA). The NSF grant was awarded to support the development of a novel technique that would allow, for the first time, high-throughput analysis of the small RNA molecules. The USDA funding is focused on the application of this technology to characterizing small RNAs in rice.

Blake C. Meyers, assistant professor of plant and soil sciences in the College of Agriculture and Natural Resources, and Pamela J. Green, Crawford H. Greenewalt Endowed Chair in Plant Molecular Biology, a joint appointment in the Department of Plant and Soil Sciences and the College of Marine Studies, are conducting the research using the Massively Parallel Signature Sequencing (MPSS) developed by Lynx Therapeutics Inc. The application of MPSS to small RNAs was pioneered by Green and Meyers in collaboration with scientists at Lynx Therapeutics.

Green and Meyers are affiliated with the Delaware Biotechnology Center, which houses their laboratories. For these projects, Green’s laboratory handles the experimental and laboratory work, and Meyers’ laboratory focuses on the computational aspects of the work. Students and scientists in the two laboratories work jointly on the analysis of the data.

RNA is the only biological polymer that can both act as a catalyst, in the manner of proteins, and store key information, like deoxyribonucleic acid (DNA). As such, it plays a key role in the life of cells.

Small RNAs are characterized by a length of approximately 21 to 24 nucleotides. The biological activity of small RNAs was first described about 12 years ago, but the most substantial advances in this field have only been made in the last six or seven years. These molecules are important to the activities of many genes, and the molecules regulate many aspects of an organism’s development and physiology.

Small RNAs have been categorized into two types, microRNAs and small interfering RNAs, that are apparently produced through different biological pathways.

These small RNAs are key to understanding development because they can “silence” genes, or keep them from being expressed. They can do this through a variety of mechanisms, including degradation of messenger RNAs that carry information from DNA and inhibition of the translation of genetic information.

DNA carries genetic instructions for the biological development of all cellular forms of life and its structure is similar to that of RNA. Some small RNAs can render the DNA inactive.

Recent advances in the study of silencing RNAs have illustrated important biological roles for both microRNAs and small interfering RNAs, Meyers said.

In the NSF-funded project, the application of MPSS to this area of research will allow for the first time the comprehensive discovery and precise quantification of microRNAs and small interfering RNAs produced in a given organism. Specific to this project are analyses of the model plant Arabidopsis, as well as initial analyses of the crop plant rice.

“The USDA-funded project, which uses the newly developed MPSS protocol, will be the first large-scale attempt to identify all small RNA molecules expressed in rice,” Meyers said. “We will assess the diversity and abundance of these molecules under normal growth conditions and under abiotic and biotic stress.” Abiotic stress involves environmental components, such as climate or drought.

Preliminary findings of the UD researchers suggest that most small RNAs have yet to be identified, Meyers said, adding, “We believe that existing methods do not sequence deeply enough to sample the full complexity of small RNAs.”

Green said the MPSS approach should not only overcome this limitation in plants but should be applicable to diverse organisms with small RNAs.

Data from the study will be publicly available through the research team’s web-based interface for rice MPSS data, which can be found at [http://mpss.udel.edu].

"This extensive set of small RNA data, along with the bioinformatics tools that we have developed for analysis and visualization, will help plant biologists understand small RNA regulation of the genome in an important crop species,” Meyers said. “Individual biologists will be able to examine the impact of small RNAs on their favorite genes of interest."

Article by Neil Thomas

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