Functions of a novel noncoding RNA family

该项目旨在了解一个新的分子家族如何控制基因的开启或关闭。与大多数已知的蛋白质基因调节因子不同，这些调节因子是核糖核苷酸链，称为非编码rna。这些特殊的ncrna是在该项目的早期工作中在模式生物秀丽隐杆线虫中发现的，这也表明它们在秀丽隐杆线虫的发育过程中具有功能。因此，这项研究将揭示对动物发育和基因调控至关重要的调控途径的新见解。此外，该项目将开发新方法，从少量材料中检测和计数数百万个RNA分子。这些方法可以广泛应用于医学诊断、新的环境调查方法或法医调查。该项目还将为研究生提供科学培训，这些研究生将把该研究作为其博士论文的一部分，并将作为对科学或科学相关职业感兴趣的本科生研究培训计划的基础。非编码rna （ncRNAs）正迅速成为令人惊讶的突出和多样化的调控因子。然而，大多数ncrna的功能是一个谜。该项目的初步研究发现了一个结合Sm环的新型ncrna家族，Sm环是在所有生命领域中发现的古老蛋白质复合物的亲戚。在真核生物中，Sm环是催化mRNA剪接的snRNA复合物的核心组分。然而，一些研究表明，Sm环还有许多其他鲜为人知的功能。总的来说，这些发现表明多个sm结合的ncRNAs控制未知的RNA靶点，从而调节各种过程。本项目将使用线虫C. elegans作为模型系统来探索这一想法。靶向基因破坏将与独特的高通量RNA测序策略和已建立的测定相结合，以确定Sm ncRNA突变如何改变RNA谱和其他生物学功能。转基因操作将测试Sm ncRNAs如何在体内控制RNA靶标的新兴模型。该项目将揭示新型ncrna的功能，这代表了一种新的，鲜为人知的遗传控制范式。研究结果可能会改变人们对Sm家族环及其ncRNA伙伴功能的认识。此外，该项目将有助于开发新的基因组尺度方法和生物信息学工具，这些方法和工具将广泛适用于从整个系统发育的基因组中出现的许多其他ncrna家族。

This project seeks to understand how a new family of molecules controls how genes are turned on or off. Unlike most known gene regulators, which are proteins, these regulators are chains of ribonucleotides called noncoding RNAs. These particular ncRNAs were discovered in the model organism C. elegans in earlier work on this project, which also suggested they have functions during C. elegans development. So, this study will reveal new insights into regulatory pathways that are critical to animal development and gene regulation. In addition, the project will develop new methods to detect and count millions of RNA molecules from small amounts of material. These methods could have broad applications including in medical diagnosis, new environmental survey methods, or forensics investigations. This project will also provide scientific training of a graduate student, who will conduct this research as part of their PhD thesis, and will serve as the basis of a research training program for undergraduate students interested in science or science-related careers.Noncoding RNAs (ncRNAs) are rapidly emerging as surprisingly prominent and diverse regulators. However, functions of most ncRNAs are a mystery. Preliminary studies for this project discovered a family of novel ncRNAs that bind Sm rings, relatives of ancient protein complexes found in all domains of life. In eukaryotes, Sm rings are core components of snRNA complexes that catalyze mRNA splicing. However, several studies suggest that Sm rings have a variety of other poorly understood functions. Collectively, these findings suggest that multiple Sm-bound ncRNAs control unknown RNA targets, thereby regulating a variety of processes. This project will explore this idea using the nematode C. elegans as a model system. Targeted gene disruption will be combined with unique high throughput RNA sequencing strategies and established assays to determine how Sm ncRNA mutations alter RNA profiles and other biological functions. Transgene manipulations will test emergent models for how Sm ncRNAs control RNA targets in vivo. This project will reveal functions of novel ncRNAs, which represent a new, poorly understood paradigm of genetic control. Results may transform ideas for the functions of Sm family rings and their ncRNA partners. In addition, this project will help develop new genome scale methods and bioinformatic tools that will have broad applicability to the many other families of ncRNAs emerging from genomes throughout phylogeny.