EAGER: Elucidating the basis of retrotransposon target preference

Penelope样元件的转座机制是真核生物中最后一个未被表征的逆迁移机制之一。建立一个易于处理的系统来剖析这些元件的机制和靶向偏好，不仅会促进我们对自然发生的基因组重排的基本理解，而且还可能有助于设计新的真核生物基因递送系统。该项目将为暑期本科生实习提供支持，以在MBL密集的夏季研究氛围中培训学生微生物学和分子生物学技术。反转录转座子是移动的遗传元件，即，插入多细胞生物基因组中的DNA片段，但可以自主复制，使用类似病毒的机制制造RNA，然后逆转录它。两个主要的逆转录转座子亚类是LTR和非LTR（LINE）逆转录转座子，第三个主要亚类命名为Penelope样元件，最近才发现，尚未得到充分研究。有趣的是，与其他两类逆转录转座子不同，Penelope样元件似乎位于基因组的那些区域，其中核苷酸序列排列成所谓的（TA）n微卫星，即，两个核苷酸的多次重复这种重复很少在活性蛋白质编码基因中发现，在这个项目中，研究人员正在寻求定义追溯元素如何“找到"整合的分子细节。这个奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

Transposition mechanisms of Penelope-like elements are one of the last uncharacterized mechanism of retromobility in eukaryotes. Establishment of a tractable system to dissect the mechanism and target preferences of these elements would not only advance our basic understanding of naturally occurring genome rearrangements but may also help design novel gene delivery systems in eukaryotes. The project will provide support for a summer undergraduate internship to train a student in microbiology and molecular biology techniques in the context of intensive summer research atmosphere at the MBL.Retrotransposons are mobile genetic elements, i.e., fragments of DNA that are inserted in the genomes of multicellular organisms, but may replicate autonomously, using virus-like mechanisms of making RNA and then reverse transcribing it. The two main retrotransposon subclasse are the LTR-and non-LTR (LINE) retrotransposons and the third major subclass, named Penelope-like elements has been found only recently and is not well-studied. Interestingly, and unlike the other two classes of retrotransposons, Penelope-like elements appear to locate in those regions of the genome where the nucleotide sequence is arranged into the so-called (TA)n microsatellites, i.e., multiple repetitions of just two nucleotides. Such repetitions are rarely found within active protein-coding genes, and in this project, researchers are seeking to define the molecular details of how the retroelements 'find' where to integrate.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.