Small RNAs play big role in genetics

The University is emerging as an important center for research on small ribonucleic acids (RNAs), which are vital in regulating genes in both plants and animals.

In recent months, UD scientists have received four major grants totaling about $4 million for research on small RNAs and have published a paper in the journal Genome Research.

The research effort into small RNAs is led by Pamela J. Green, Crawford H. Greenewalt Endowed Chair in Plant Molecular Biology, and Blake C. Meyers, associate professor of plant and soil sciences, both faculty members with offices and research laboratories at the nearby Delaware Biotechnology Institute.

RNA is the only biological polymer that can both act as a catalyst, in the manner of proteins, and also store key information, like deoxyribonucleic acid (DNA). As such, it plays an important role in the life of cells. Small RNAs are characterized by a length of approximately 21 to 24 nucleotides.

Green calls small RNAs “one of most important discoveries in biotechnology in the last 10 years” because they play a crucial role in regulating genes in plants and animals. Deficiencies in small RNA production can have a profound effect on development, and small RNAs have been associated with other important biological processes, such as responses to stress.

Determining the sequence of the small RNAs of an organism is critical for understanding their overall impact and individual biological roles, Meyers says, and the researchers have pioneered studies of small RNA by using novel technologies to generate the data combined with computational approaches to analyze it. They are working with several competing technologies—from Solexa Inc. and 454 Life Sciences Inc.— to characterize the diversity and expression patterns of transcripts.

The National Science Foundation recently announced a grant of $1.1 million to the two researchers for a project to develop extensive sequence resources of small RNAs and target messenger RNAs from representative species across the plant kingdom. The information gained will enable functional and evolutionary studies of two classes of RNAs—known as microRNAs (miRNAs) and short-interfering RNAs (siRNAs).

Most studies have been limited to the plant Arabidopsis, a weed from the mustard family, which is important because its rapid growth cycle and small size make it an ideal experimental model for plant biology research. However, the little that is known about small RNA diversity and evolution suggests that miRNAs are a well-conserved gene regulatory system dating back to lower plants and potentially to green algae.

The new project will develop an unparalleled resource of millions of plant small RNAs for comparative analyses, derived from 32 different plant species, Meyers says.

Earlier last year, Green and Meyers received a $500,000 National Science Foundation award to build on work they reported in a September 2005 issue of the journal Science. Through deep sequencing of Arabidopsis, the team discovered 10 times more small RNAs than had previously been identified.

Through the funding, the researchers plan to look closely at miRNAs and siRNAs and their role in environmental stress, such as drought and cold. Green says that because many Arabidopsis miRNAs are conserved in rice and other plants, this work should lead to the discovery of new functions of general significance.

These new small RNA sequencing and analysis techniques developed at the University are being put to use in other plant genomes. Janine Sherrier, associate professor of plant and soil sciences housed at DBI, has received $500,000 through the U.S. Department of Agriculture’s national research initiative plant genome program to sequence small RNAs in Medicago. This project is in collaboration with Green and Meyers and builds off the three investigators’ combined skills in Medicago biology, small RNAs and genomic analyses.

Medicago is closely related to alfalfa and thus a good model for such legumes as soybeans, an important crop in Delaware, and such common beans as kidney and black beans.

Meyers says these plants are interesting and of great agronomic importance because they can “fix” their own nitrogen. This ability is unlike many other plants that require the addition of nitrogen fertilizer, which is becoming more expensive and for which there are environmental issues.

In another venture supported by the National Science Foundation, Meyers and Li Liao, assistant professor of computer and information sciences, are co-principal investigators on a new $1.9 million DNA sequencing project led by W. Richard McCombie of Cold Spring Harbor (N.Y.) Laboratory.

The project is aimed at assessing several new technologies available to sequence genomic DNA.

—Neil Thomas, AS ’76