Micro-RNA in oral tissues
Mapping miRNAs expressed during development of oral tissues. Functions of miRNAs expressed during development.
About the project
MicroRNAs (miRNAs) represent an abundant class of short, non-coding RNAs (~ 22 nucleotides), the likely key function of which is to regulate gene expression at a post-transcriptional level. By binding to target mRNAs, miRNAs induce mRNA decay or translation repression. The degree of complementarity between a miRNA and its target may determine whether the miRNA will block protein biosynthesis by mRNA decay or by inhibition of translation.Several miRNA-binding sites are needed for efficient translation repression. It has been suggested that targets with a single miRNA-binding site may lead to “fine tuning” of mRNA activity. Several studies indicate that miRNAs may be vital during embryogenesis 12-15. Many miRNAs appear to be expressed in a tissue- and organ-specific manner, especially during development when their expression is regulated in a time-dependent fashion. MiRNA expression profiling of developing oral tissues is essential to understand miRNA function during development.
Studies of craniofacial development have so far mostly focused on DNA, mRNA and proteins, whereas the role of epigenetic factors, e.g., non-coding RNAs (ncRNAs), is unexplored. No data on miRNA levels in oral tissues appears available. We have, therefore, studied miRNA expression in the developing first molar tooth germ and in the developing submandibular salivary gland. MiRNA expression profiling of the developing murine first molar mandibular tooth germ and the developing submandibular salivary gland is carried out using microarrays and real-time PCR. Clusters of miRNAs selected from expression profiles were also subjected to bioinformatic analysis. So far, over 2000 coding genes have been found to be expressed during odontogenesis. These study suggests that miRNAs are also likely to be involved, perhaps by modulating activities of mRNAs coding for proteins regulating transcription/RNA processing. Mandibular administration of a novel class of chemically engineered oligonucleotides termed “antagomirs” resulted in a marked decrease in level of corresponding miRNA in the tooth germ, and significantly altered expression of more than 1000 genes. Levels of several of the encoded protein are also signficantly altered. The mechanisms mediating such changes is not clear. However, it may involve an indirect effect (the suppression of a transcriptional repressor), or alternatively, miRNA may have a direct effect on gene activation (e.g. chromatin remodeling).
This project has been active for three years; financially supported by faculty.