权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Engineered Regulated RNA Localization and Transport in Biological Systems

生物系统中工程调控的 RNA 定位和运输

基本信息

批准号：
7981032
负责人：
JACQUIN C NILES
金额：
$ 251.25万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
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：
2010-09-30 至 2015-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (Provided by the applicant) Abstract: Evidence is rapidly accumulating in support of specific and functionally significant sub- cellular mRNA localization in many organisms. Transcript localization shapes many fundamental processes including cell polarity, migration and neuronal activity, and impacts diverse biological processes such as development, memory and learning. Although attention has been focused on localization of a few selected transcripts, recent global analyses indicate that the phenomenon is extremely common. In many cases, different transcripts are observed to have distinct sub-cellular spatial localization patterns. Several prominent examples of specific transcript localization shaping processes such as body axis polarity in Drosophila and synaptic plasticity in neurons suggest the potential for there being direct functional significance of transcript localization, now recognized to be a commonly observed phenomenon. Unfortunately, we have very limited understanding of the protein factors required for achieving specific transcript localization patterns. Moreover, we lack strategies for selectively perturbing transcript spatial distribution in a manner compatible with understanding the associated functional consequences. This proposal addresses these needs by introducing a method permitting regulated targeting of a given transcript to a sub-cellular location, the latter being driven by known or putative localization factors under evaluation. In this approach, transcript localization is entirely experimentally controlled, and is conditional upon either small molecule or peptide signals applied to target cells using high-resolution chemical gradients and post-translational protein localizing modifications, respectively. This broadly applicable method has the potential to advance our basic knowledge of the cellular mechanisms underlying transcript localization, and to probe the associated functional implications at both the cellular and organism levels. Public Health Relevance: Sub-cellular RNA localization into discrete, transcript-dependent patterns is now recognized to be a widespread phenomenon in many cell types and organisms, including humans. In several well-studied cases, transcript localization is required for establishing proper cellular function, and defects in this process contribute to developmental, cognitive and other neurological problems in humans. The proposed research will introduce new methods for understanding and manipulating the mechanisms underlying RNA sub-cellular localization, and has the potential to improve both our understanding and treatment of disease processes associated with RNA localization defects.

描述（由申请人提供）翻译后摘要：证据正在迅速积累，在许多生物体中的特定和功能显着的亚细胞mRNA定位的支持。转录本定位塑造了许多基本过程，包括细胞极性、迁移和神经元活动，并影响了多种生物过程，如发育、记忆和学习。虽然注意力一直集中在少数选定的成绩单本地化，最近的全球分析表明，这种现象是非常普遍的。在许多情况下，观察到不同的转录物具有不同的亚细胞空间定位模式。一些突出的例子，具体的转录本本地化的形成过程，如体轴极性在果蝇和神经元突触可塑性表明，有直接的功能意义的转录本本地化的潜力，现在被认为是一个普遍观察到的现象。不幸的是，我们对实现特定转录本定位模式所需的蛋白质因素的理解非常有限。此外，我们缺乏选择性地扰乱转录本的空间分布的方式与理解相关的功能后果兼容的策略。该提议通过引入允许将给定转录物调节靶向亚细胞位置的方法来解决这些需求，后者由正在评估的已知或推定的定位因子驱动。在这种方法中，转录本定位完全由实验控制，并且分别取决于使用高分辨率化学梯度和翻译后蛋白定位修饰施加于靶细胞的小分子或肽信号。这种广泛适用的方法有可能推进我们的基本知识的转录本本地化的细胞机制，并探测相关的功能在细胞和生物体水平的影响。公共卫生相关性：亚细胞RNA定位成离散的、转录依赖的模式现在被认为是许多细胞类型和生物体（包括人类）中的普遍现象。在几个充分研究的情况下，转录本定位是建立适当的细胞功能所必需的，并且该过程中的缺陷有助于人类的发育，认知和其他神经问题。拟议的研究将引入新的方法来理解和操纵RNA亚细胞定位的机制，并有可能提高我们对与RNA定位缺陷相关的疾病过程的理解和治疗。