Collaborative Research: SG: piRNA Dynamics in the Absence of Active Transposable Elements
Collaborative Research: SG: piRNA Dynamics in the Absence of Active Transposable Elements
批准号:
1355176
负责人:
David Ray
金额:
$5.59万
依托单位:
依托单位国家:
美国
项目类别:
Standard Grant
财政年份:
2014
资助国家:
美国
项目状态:
已结题
起止时间:
2014-04-15 至 2017-03-31
中文摘要
转座元件(TES)是DNA序列,具有通过剪切和粘贴或复制和粘贴机制在基因组中移动和复制的能力。TE是脊椎动物基因组的主要组成部分,至少占人类基因组的45%。由于TES的不受限制的增殖可能具有深远的,而且大多是有害的生物效应,因此生物如何控制TES动员的问题引起了人们的高度兴趣。实验数据表明,TES和最近发现的一类称为piRNAs的小型非编码RNA,参与了一场进化的军备竞赛,类似于病原体和免疫系统的军备竞赛。简而言之,piRNAs引导蛋白质对抗TE产生的信使RNA。然而,piRNAs和TES之间相互作用的细节还远不清楚。本项目的研究目标是通过与具有持续TE活性的小鼠进行比较,来表征缺乏持续TE活性的沙鼠中的piRNA谱带。了解基因组如何保护自己免受TE入侵的挑战是进化基因组学中的一个基本问题。这个项目代表着朝着这个方向迈出的一步。TES具有改变基因及其表达的能力,因此它们可以产生深远的生物效应。此外,piRNA途径在生物技术和医学方面具有巨大的应用潜力。如果研究人员能够引导这一途径,他们应该能够瞄准有害的基因变异,例如那些与癌症有关的基因变异,这个项目将有助于实现这一长期目标。此外,该项目还将对年轻的生物信息学研究人员进行培训。
英文摘要
Transposable elements (TEs) are DNA sequences with the ability to move and make copies in a genome through -cut and paste- or -copy and paste- mechanisms. TEs are major components of vertebrate genomes, and account for at least 45% of the human genome. Because the unrestricted proliferation of TEs can have profound, and mostly deleterious, biological effects, the question of how organisms control TE mobilization has attracted high interest. Experimental data suggest that TEs and a recently discovered class of small non-coding RNAs called piRNAs, are involved in an evolutionary arms race, similar to that of pathogens and the immune system. Briefly, piRNAs direct proteins against TE derived messenger RNAs. However, the details of the interplay between piRNAs and TEs are far from clear. The research objective of this project is to characterize piRNA repertoires in the ground squirrel, which lacks ongoing TE activity, by contrasting them with mouse which have ongoing TE activity.Understanding how genomes protect themselves from the challenges presented by TE invasion is a fundamental question in evolutionary genomics. This project represents a step in that direction. TEs have the ability to change genes and their expression, and as such they can have profound biological effects. In addition, the piRNA pathway has enormous potential for applications in biotechology and medicine. If the investigators are able to direct this pathway, they should be able to target deleterious gene variants, such as those involved in cancer, and this project will contribute towards this long term objective. In addition, this project will permit the training of young researchers in bioinformatics.
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