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

摘要 腭裂的发生受多种复杂的遗传和环境因素的影响。在味觉中 在形态发生过程中，数百个基因的表达在每个胚胎阶段都会发生巨大的变化。然而，它是 在很大程度上仍然不清楚这些基因表达是如何调控的。最近的研究表明，非编码RNA (ncRNAs：98%的转录组)影响由编码RNA(又名信使)编码的基因的表达 RNAs，mRNAs)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mRNAs进行交易的，但大多数 基因组转录成ncRNAs，包括microRNAs(MiRs)和长非编码RNAs(LncRNAs)。我们 假设适当地控制ncRNAs，它在味觉发育中起着重要作用，对于 对基因的调节，因为它们的破坏会导致腭裂。识别涉及到的ncRNAs 我们将分析1)FaceBase1 miR测序(miR-seq)数据集；2)FaceBase1mRNA 微阵列数据集；以及3)来自发育中的小鼠的FaceBase1 RNA测序(RNA-seq)数据集 味觉。此外，从之前的人类遗传学研究中预测与腭裂有关的ncRNAs 对于小鼠，我们将对腭裂的致病基因进行系统的综述和荟萃分析。调查结果由 然后，生物信息学分析将得到实验验证。我们的具体目标是1)确定基因 以及它们在腭部发育过程中受miRs调控的功能；2)鉴定参与腭部发育的lncRNAs 以及3)确定ncRNAs与表型的直接生物学联系。这项研究将提供 洞察ncRNAs在腭部发育中的作用，并提出可能的诊断和治疗策略 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.