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Identification and Functional Characterization of Zebrafish microRNAs

斑马鱼 microRNA 的鉴定和功能表征

基本信息

批准号：
7924413
负责人：
James G. Patton
金额：
$ 14.11万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7924413
关键词：
3&apos Untranslated Regions Antisense Oligonucleotides Automobile Driving Bioinformatics Biotin Cell physiology Cells Cloning Code Data Defect Development Disease Embryo Embryonic Development Eukaryotic Cell Fishes Gastrula Gene Expression Gene Expression Regulation Gene Family Genes Genetic Screening Germ Layers Glean Goals Human In Situ Hybridization In Vitro Incubated Injection of therapeutic agent Label Mediating Messenger RNA MicroRNAs Normal Cell Northern Blotting Oligodendroglia Pattern Phenotype Protein Isoforms Proteins RNA Reporter Research Personnel Ribosomal RNA Role Sorting - Cell Movement System Testing Tissues Transfer RNA Transgenic Organisms Translational Repression Untranslated RNA Zebrafish base cell type gain of function gastrulation insight interest loss of function mutant nerve stem cell novel numb protein programs promoter research study streptavidin-agarose zebrafish development zygote

项目摘要

DESCRIPTION (provided by applicant): Multiple eukaryotic sequencing projects have led to the surprising finding that the number of protein coding genes is far less than that predicted based on total protein content. This underscores the fact that regulation of gene expression is crucial to enable a relatively limited number of genes to encode a wide array of protein isoforms in a tissue- and developmental-specific pattern. Within the last couple of years, it has become apparent that focusing on just protein coding genes ignores genes for noncoding RNAs which appear to make up more than 1% of the total number of genes. Several classes of RNA are well known (tRNA, mRNA, and rRNA) but perhaps the most interesting class of noncoding RNAs includes a family of genes referred to as microRNAs (miRNAs). miRNAs function to regulate gene expression in a sequence specific manner by either degrading target mRNAs or by mediating translational repression. In this proposal, we seek to globally identify all zebrafish miRNAs and determine their cell-, tissue-, and developmental-specific expression patterns using a novel microarray strategy. Eukaryotic cells encode approximately 250-300 miRNAs yet the targets of these RNAs are almost entirely unknown. Using the array data, we will identify miRNA targets and examine the phenotypic consequences of miRNA gain-of-function and loss-of-function. The fact that miRNAs have only recently been identified illustrates the difficulty of identifying all genes using forward genetic screens, especially small vertebrate genes such as those encoding miRNAs. It has been estimated that 10% or more of eukaryotic genes might be regulated by one or more miRNAs and the goal of this proposal is to use the zebrafish system to answer questions about how miRNAs regulate early development. Because miRNAs are highly conserved, it seems certain that information gleaned using zebrafish will be directly applicable to humans and uncover potential roles for human miRNAs in normal cell function, development, and disease.

描述（由申请人提供）：多个真核生物测序项目令人惊讶地发现，蛋白质编码基因的数量远远少于根据总蛋白质含量预测的数量。这强调了这样一个事实，即基因表达的调控对于使相对有限数量的基因在组织和发育特异性模式中编码广泛的蛋白质同种异构体至关重要。在过去的几年里，很明显，只关注蛋白质编码基因忽略了非编码rna的基因，而非编码rna似乎占基因总数的1%以上。有几类RNA是众所周知的（tRNA， mRNA和rRNA），但也许最有趣的一类非编码RNA包括一个被称为microrna （miRNAs）的基因家族。miRNAs通过降解靶mrna或介导翻译抑制，以序列特异性方式调节基因表达。在本提案中，我们寻求全球鉴定所有斑马鱼mirna，并使用一种新的微阵列策略确定其细胞，组织和发育特异性表达模式。真核细胞编码大约250-300个mirna，但这些rna的靶点几乎完全未知。利用阵列数据，我们将确定miRNA靶点，并检查miRNA功能获得和功能丧失的表型后果。mirna直到最近才被鉴定，这一事实说明了使用正向遗传筛选鉴定所有基因的困难，特别是那些编码mirna的小型脊椎动物基因。据估计，10%或更多的真核生物基因可能受到一个或多个mirna的调节，本提案的目标是利用斑马鱼系统来回答有关mirna如何调节早期发育的问题。由于mirna是高度保守的，从斑马鱼身上收集到的信息似乎可以肯定将直接适用于人类，并揭示人类mirna在正常细胞功能、发育和疾病中的潜在作用。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

miR-27 regulates chondrogenesis by suppressing focal adhesion kinase during pharyngeal arch development.

DOI：
10.1016/j.ydbio.2017.06.013
发表时间：
2017-09-01
期刊：
Developmental biology
影响因子：
2.7
作者：
Kara N;Wei C;Commanday AC;Patton JG
通讯作者：
Patton JG

The role of miR-124a in early development of the Xenopus eye.

miR-124a 在非洲爪蟾眼睛早期发育中的作用

DOI：
10.1016/j.mod.2009.08.002
发表时间：
2009-10
期刊：
MECHANISMS OF DEVELOPMENT
影响因子：
2.6
作者：
Qiu, Rong;Liu, Kaili;Liu, Ying;Mo, Weichuan;Flynt, Alex S.;Patton, James G.;Kar, Amar;Wu, Jane Y.;He, Rongqiao
通讯作者：
He, Rongqiao

Transcriptome-wide analysis of small RNA expression in early zebrafish development.