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

摘要 腭裂的病因受到多种复杂的遗传和环境因素的影响。上颚期间 形态发生，数百个基因的表达显着变化，在每个胚胎阶段。但据 这些基因的表达是如何被调控的，在很大程度上仍不清楚。最近的研究表明，非编码RNA （ncRNA：转录组的98%）影响编码RNA（又名信使）编码的基因表达 RNA，mRNA）以及表型而不改变DNA序列，并有助于许多 疾病虽然大多数遗传信息是由蛋白质通过mRNA进行处理的，但大多数遗传信息是由蛋白质通过mRNA进行处理的。 基因组被转录成ncRNA，包括microRNA（miR）和长链非编码RNA（lncRNA）。我们 假设在腭发育中起重要作用的ncRNA的适当控制对于 基因的调节，因为它们的破坏会导致腭裂。为了鉴定参与的ncRNA， 腭发育，我们将分析1）FaceBase 1 miR测序（miR-seq）数据集; 2）FaceBase 1 mRNA 微阵列数据集;和3）FaceBase 1 RNA测序（RNA-seq）数据集，来自发育中的小鼠 上颚此外，为了从先前的人类遗传学研究中预测与腭裂相关的ncRNA， 小鼠，我们将对腭裂致病基因进行系统回顾和荟萃分析。的发现 生物信息学分析将通过实验验证。我们的具体目标是：1）确定 以及它们在腭部发育过程中受miR调控的功能; 2）鉴定与腭部发育相关的lncRNA 3）确定ncRNA与表型的直接生物学联系。本研究将提供 深入了解ncRNA在腭发育中的作用，并提出可能的诊断策略， 预防腭裂。

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.