Regulatory Targets of Nematode MicroRNAs

Health Research Incorporated/New York State Department Of Health, Menands NY

Investigators

Abstract

Wadsworth Center is awarded a project to develop new statistical methods for genome-wide identification of MicroRNAs. MicroRNAs (miRNAs) are small non-coding RNAs of ~22 nucleotides that repress translation of target messenger RNAs (mRNAs) in multi-cellular eukaryotes. The first miRNA, lin-4, was discovered in C. elegans by the Ambros lab in 1993. Since then, experimental and computational studies have discovered thousands of miRNAs in animals. Emerging evidence suggests a widespread impact of mammalian miRNAs on translational regulation. The reliable identification of miRNA targets is essential for fully understanding this new dimension of the complex gene regulatory networks. The objectives of this project include: 1) the development of novel statistical methods for genome-wide miRNA target identification in nematodes; 2) in vivo experimental testing in C. elegans for validation of predicted nematode targets; and 3) the development and maintenance of an online nematode miRNA target database. The methods developed here for nematodes are expected to serve as a foundation for developing improved methods for miRNA target prediction for human and other vertebrates via genome-specific modifications and extensions and experimental validation. The project will provide excellent opportunity for interdisciplinary training of post-doctoral fellows and computational scientists in the burgeoning field of computational biology. The nematode miRNA target database will include both validated and predicted targets. The availability of such an information infrastructure will facilitate new miRNA target discovery, and will be valuable for eventual complete understanding of miRNA functions in gene regulation.