The ultimate goal of this research is to develop models to predict the structure of RNA molecules from their sequence. Many defects in cellular processes are mediated through RNA, and the ability to predict their structure will lead to the rational design of drugs. The specific aim of this research is to characterize the thermodynamic stability of RNA duplexes containing bulge and hairpin loops. These studies will combine both thermodynamic and structural characterization of the RNA duplexes to achieve a better understanding of the nature of RNA loops. RNAs are intimately involved in a wide variety of biological activities. During the process of gene expression, they serve as both the informational molecules and as part of the decoding machinery. Biological molecules, including RNA, must fold into the correct three-dimensional shape to acquire their active-functional form. The ability to predict RNA structure from sequence will improve our understanding of RNA and its biological role. Undergraduate students will perform all of the investigations, including the selection of sequences to be investigated, providing them with excellent training and valuable research experience. This work will be disseminated both as published manuscripts in peer-reviewed journals and at scientific meetings including regional and national ACS meetings.

Project Report

Award ID: 0744631 Introduction: The research objective of this proposal was to improve methods for predicting the structure of RNA from sequence. Specifically we examine the stability of small model RNA molecules with defined structural characteristics. Changes in the sequence of the RNAs are then correlated to the relative stability of the RNA to develop rules to predict the stability of naturally occurring RNAs from their sequence. The research is done by undergraduate students as part of their senior project and summer research experiences. These experiences increase the students’ interest in graduate school and research in general. Research results summary: The outcomes of this work have resulted in improved methods to predict the folding of RNA. Specifically our results have led to improvements in the prediction of the stability of ends and of unpaired nucleotides of the RNA duplex which will help in understanding RNA folding and interactions. Additionally, we have developed a fluorescent in-line probing method for the structural analysis of small RNAs. This procedure allows us to distinguish which of two identical nucleotides in a bulge is in fact unpaired. This project was primarily done by 20 undergraduate students who gained training in independent research. Twelve of these students were coauthors on published manuscripts. In addition, 11 of these students presented their work at national or regional conferences. Seven of the students who have graduated are currently attending professional schools and nine are attending graduate school.

Agency
National Science Foundation (NSF)
Institute
Division of Molecular and Cellular Biosciences (MCB)
Application #
0744631
Program Officer
Roy Welch
Project Start
Project End
Budget Start
2008-03-01
Budget End
2011-09-30
Support Year
Fiscal Year
2007
Total Cost
$203,115
Indirect Cost
Name
Allegheny College
Department
Type
DUNS #
City
Meadville
State
PA
Country
United States
Zip Code
16335