Characterization and Identification of MicroRNA Core Promoters in Four Model Species

Abstract

MicroRNAs are short, noncoding RNAs that play important roles in post-transcriptional gene regulation. Although many functions of microRNAs in plants and animals have been revealed in recent years, the transcriptional mechanism of microRNA genes is not well-understood. To elucidate the transcriptional regulation of microRNA genes, we study and characterize, in a genome scale, the promoters of intergenic microRNA genes in Caenorhabditis elegans, Homo sapiens, Arabidopsis thaliana, and Oryza sativa. We show that most known microRNA genes in these four species have the same type of promoters as protein-coding genes have. To further characterize the promoters of microRNA genes, we developed a novel promoter prediction method, called common query voting (CoVote), which is more effective than available promoter prediction methods. Using this new method, we identify putative core promoters of most known microRNA genes in the four model species. Moreover, we characterize the promoters of microRNA genes in these four species. We discover many significant, characteristic sequence motifs in these core promoters, several of which match or resemble the known cis-acting elements for transcription initiation. Among these motifs, some are conserved across different species while some are specific to microRNA genes of individual species.

Author Summary

MicroRNAs are a class of short RNA sequences that have many regulatory functions in complex organisms such as plants and animals. However, our knowledge of the transcriptional mechanisms of microRNA genes is limited. Here, we analyze the upstream sequences of known microRNA genes in four model species, i.e., C. elegans, H. sapiens, A. thaliana, and O. sativa, and compare them with the promoter sequences of protein-coding genes and other classes of RNA genes. This analysis provides genome-wide evidence that microRNA genes have the same type of promoter sequences as protein-coding genes, and therefore are likely transcribed by RNA polymerase II (pol II). Second, we present a novel computational method for promoter prediction, which is then applied to locate the core promoters of known microRNA genes in the four model species. Furthermore, we present an analysis of short DNA motifs that appear frequently in the predicted promoters of microRNA genes, and report several interesting motifs that may have some functional meanings. These results are important for understanding the initiation and regulation of microRNA gene transcription.