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

上颚发育中非编码 RNA 靶向的转录本和功能

• 批准号: 9333364
• 负责人: Junichi Iwata
• 金额: $ 23.1万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9333364
• 关键词: Affect; Alpha Cell; Anterior; Base Sequence; Bioinformatics; Biological; Cell Count; Cell Proliferation; Cell Survival; Cells; Cleft Palate; Code; Complex; DNA Sequence; Data; Data Analyses; Data Set; Databases; Development; Diagnosis; Disease; Early Diagnosis; Embryo; Environmental Risk Factor; Ethnic Origin; Etiology; Event; Family; Future; Gender; Gene Expression; Gene Expression Regulation; Gene Mutation; Gene Targeting; Genes; Genetic; Genetic Research; Genetic study; Genome; Goals; Health; Hour; Human; Image; In Situ Hybridization; Individual; Internet; Lateral; Lead; Linear Models; Link; Medial; Mesenchymal; Messenger RNA; Meta-Analysis; MicroRNAs; Morphogenesis; Mus; Organ; Palate; Pattern; Phenotype; Play; Population; Prevalence; Prevention; Process; Proteins; Quality Control; Quantitative Reverse Transcriptase PCR; RNA; RNA-Protein Interaction; Reverse Transcriptase Polymerase Chain Reaction; Role; Scanning Electron Microscopy; Specificity; Structure; Technology; Testing; Therapeutic; Tissues; Transact; Transcript; Translating; Untranslated RNA; Variant; base; design; differential expression; experimental study; genetic approach; genetic information; genome-wide; human genome sequencing; insight; mRNA Expression; overexpression; palatogenesis; prevent; public health relevance; systematic review; tool; transcriptome; transcriptome sequencing

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.

抽象的 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 在形态发生过程中，数百个基因表达在每个胚胎阶段都会发生巨大变化。然而，它是 目前仍不清楚这些基因表达是如何调节的。最近的研究表明，非编码 RNA （ncRNA：98% 的转录组）影响编码 RNA（又名信使）编码的基因的表达 RNA、mRNA）以及表型，而不改变 DNA 序列，并有助于许多 疾病。尽管大多数遗传信息是通过 mRNA 由蛋白质进行处理的，但大多数 基因组被转录为 ncRNA，包括 microRNA (miR) 和长非编码 RNA (lncRNA)。我们 假设 ncRNA 在上颚发育中发挥重要作用，对其进行适当控制对于 基因的调节，因为基因的破坏会导致腭裂。鉴定参与的 ncRNA 味觉发育，我们将分析 1) FaceBase1 miR 测序 (miR-seq) 数据集； 2) FaceBase1 mRNA 微阵列数据集； 3) FaceBase1 RNA 测序 (RNA-seq) 数据集，来自发育中的小鼠 味觉。此外，根据之前的人类基因研究预测与腭裂相关的 ncRNA 小鼠，我们将对腭裂致病基因进行系统回顾和荟萃分析。调查结果由 然后将通过实验验证生物信息学分析。我们的具体目标是 1) 确定基因 及其在上颚发育过程中受 miR 调节的功能； 2) 识别与上颚相关的lncRNA 发展; 3) 确定 ncRNA 与表型的直接生物学联系。这项研究将提供 深入了解 ncRNA 在上颚发育中的作用，并提出诊断和治疗的可能策略 预防腭裂。