Transcripts and Functions Targeted by Non-coding RNAs in Palate Development

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ABSTRACT The cause of cleft palate is influenced by multiple complex genetic and environmental factors. During palate morphogenesis, hundreds of gene expressions dramatically change at each embryonic stage. However, it is still largely unknown how these gene expressions are regulated. Recent studies reveal that non-coding RNAs (ncRNAs: 98% of transcriptome) affect the expression of genes encoded by coding RNAs (aka messenger RNAs, mRNAs) as well as the phenotype without altering the DNA sequence, and contribute to a number of diseases. Although most genetic information is transacted by proteins through mRNAs, the majority of the genome is transcribed into ncRNAs including microRNAs (miRs) and long non-coding RNAs (lncRNAs). We hypothesize that the proper control of ncRNAs, which play important roles in palate development, is crucial for the regulation of genes, due to the fact that their disruption causes cleft palate. To identify ncRNAs involved in palate development, we will analyze 1) FaceBase1 miR sequencing (miR-seq) datasets; 2) FaceBase1 mRNA microarray datasets; and 3) FaceBase1 RNA sequencing (RNA-seq) datasets, from the developing mouse palate. In addition, to predict ncRNAs involved in cleft palate from previous genetic studies in humans and mice, we will perform systematic review and meta-analyses for cleft palate causative genes. The findings by bioinformatics analyses will then be validated experimentally. Our specific aims are to 1) determine the genes and their functions regulated by miRs during palate development; 2) identify lncRNAs involved in palate development; and 3) determine the direct biological link of ncRNAs to the phenotype. This study will provide insight into the role of ncRNAs in palate development and suggest possible strategies for the diagnosis and prevention of cleft palate.