Characterization of Small Silencing RNAs in Emiliania Huxleyi

艾米利亚赫胥黎小沉默 RNA 的表征

基本信息

批准号：
7852271
负责人：
Xiaoyu Zhang
金额：
$ 10.38万
依托单位：
CALIFORNIA STATE UNIVERSITY SAN MARCOS
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7852271
关键词：
Algae Animals Attention Binding Bioinformatics Biological Models Biology Biotechnology Bone Diseases Calcified Calcium Carbonate California Carbon Cell physiology Cells Chlamydomonas reinhardtii Collaborations Communities Computational Biology Computing Methodologies Data Data Set Development Disease Eukaryota Faculty Family Functional RNA Funding Gene Expression Gene Expression Regulation Gene Targeting Genome Genome Stability Goals Grant Guanine + Cytosine Composition Health Heart Diseases Human Industry Institutes Interdisciplinary Study Joints Journals Kidney Calculi Knowledge Lead Marines Messenger RNA Methods MicroRNAs Modeling Nucleotides Omega-3 Fatty Acids Organism Osteogenesis Paper Pathway interactions Peer Review Pharmacologic Substance Phytoplankton Plants Play Polysaccharides Process Proteins Publishing RNA Interference RNA Sequences Race Reading Research Research Infrastructure Role Sculpture Small Interfering RNA Small RNA Source Specificity Stress Structure Students Sulfur Therapeutic Translations Universities Validation Work atmospheric carbon dioxide base biomineralization calcification climate change design gene function human DICER1 protein insight meetings member nuclease professor programs protein expression public health relevance research study response

项目摘要

DESCRIPTION (provided by applicant): Coccolithophorids are marine phytoplanktons that produce elegantly sculptured calcium carbonate cell coverings known as coccoliths. Emiliania huxleyi (E. huxleyi) is a model coccolithophorid that has potential biomedical applications related to bone formation and diseases. Small silencing RNAs (smRNAs) are known to play a pivotal role in post transcriptional gene regulation in many eukaryotes, from unicellular to multicellular plants and animals. Small RNAs are involved in a variety of cellular processes that are essential to genome stability, development, and adaptive responses to environmental stress. These natural smRNA silencing processes otherwise known as RNA interference, suppress protein expression by triggering the enzymatic cleavage of mRNAs. The specificity of smRNA processes has been exploited for the systematic analysis of gene functions and potential therapeutic purposes. MicroRNAs (miRNAs) and small interfering RNAs (siRNAs) are two major classes of smRNAs known in plants. Very little is currently known about smRNAs and their regulatory roles in E. huxleyi. The specific hypothesis underlying this proposed research is that E. huxleyi contains small RNAs such as miRNAs and siRNAs, which regulate target genes through RNA silencing. The recent release of the E. huxleyi genome by the Joint Genome Institute (JGI) and a large dataset of small RNAs of E. huxleyi generated using high-throughput Solexa sequencing, make it feasible to systematically characterize smRNAs and their regulatory roles in E. huxleyi. Preliminary studies show strong evidence for the existence of miRNAs in E. huxleyi. We propose herein to characterize small RNAs in E. huxleyi using computational methods, combined with experimental validation. Specifically, we propose to 1) identify and characterize miRNA precursors and mature miRNAs in E. huxleyi by computationally analyzing the short RNA sequences; 2) computationally predict and characterize targets of E. huxleyi miRNAs and validate the predictions with experimental evidences; and 3) identify and characterize siRNAs and other classes of small RNAs in E. huxleyi. To our knowledge, this proposed research will be the first systemic analysis of smRNAs in E. huxleyi, and as such will provide important insights into post-transcriptional gene regulation in this microalga. PUBLIC HEALTH RELEVANCE: Coccolithophorids are presently being investigated by the biotechnology industry as a potential source for new pharmaceuticals, omega-3 fatty acids, biofuel, and polysaccharides. They also have important implications for human health in terms of understanding the process of calcification as it relates to bone disease, kidney stones, and heart disease. Insights into smRNA controlled gene regulation in E. huxleyi may lead to a better understanding of the fundamental biology of this important microcalcifier, which may offer new strategies to promote healthy biomineralization and mitigate calcification associated with disease states.

描述（由申请人提供）：颗石藻是海洋浮游植物，可产生精美的碳酸钙细胞覆盖物，称为颗石藻。赫胥黎艾米利亚 (E. huxleyi) 是一种模型球石藻，在骨形成和疾病方面具有潜在的生物医学应用。众所周知，小沉默 RNA (smRNA) 在许多真核生物（从单细胞到多细胞植物和动物）的转录后基因调控中发挥着关键作用。小RNA参与多种细胞过程，这些过程对于基因组稳定性、发育和对环境压力的适应性反应至关重要。这些天然的 smRNA 沉默过程也称为 RNA 干扰，通过触发 mRNA 的酶裂解来抑制蛋白质表达。 smRNA 过程的特异性已被用于基因功能和潜在治疗目的的系统分析。 MicroRNA (miRNA) 和小干扰 RNA (siRNA) 是植物中已知的两大类 smRNA。目前，人们对 smRNA 及其在赫胥氏大肠杆菌中的调节作用知之甚少。这项研究的具体假设是 E. huxleyi 含有小 RNA，如 miRNA 和 siRNA，它们通过 RNA 沉默来调节靶基因。联合基因组研究所 (JGI) 最近发布了赫胥黎大肠杆菌基因组，以及使用高通量 Solexa 测序生成的赫胥黎大肠杆菌小 RNA 大型数据集，使得系统地表征 smRNA 及其在大肠杆菌中的调控作用成为可能。赫胥黎。初步研究显示有力的证据证明赫胥氏埃里虫中存在 miRNA。我们在此建议使用计算方法并结合实验验证来表征 E. huxleyi 中的小 RNA。具体来说，我们建议 1) 通过计算分析短 RNA 序列来识别和表征 E. huxleyi 中的 miRNA 前体和成熟 miRNA； 2) 通过计算预测和表征 E. huxleyi miRNA 的靶标，并用实验证据验证预测； 3) 鉴定和表征赫胥氏埃里虫中的 siRNA 和其他类别的小 RNA。据我们所知，这项拟议的研究将是首次对赫胥氏巨藻的 smRNA 进行系统分析，因此将为这种微藻的转录后基因调控提供重要的见解。公共卫生相关性：目前正在研究 Coccolithophorids 生物技术产业作为新药物、omega-3 脂肪酸的潜在来源，生物燃料和多糖。它们还对人类健康产生重要影响了解钙化过程，因为它与骨病、肾结石和心脏病。深入了解赫胥黎 E. smRNA 控制的基因调控可能会带来更好的结果了解这种重要的微钙化剂的基本生物学，这可能会提供新的策略来促进健康的生物矿化和减轻与钙化相关的钙化疾病状态。