Genetic Information Research Institute, Mountain View, California, United States of America.
PLoS One. 2013 Jul 9;8(7):e68260. doi: 10.1371/journal.pone.0068260. Print 2013.
Target-specific integration of transposable elements for multicopy genes, such as ribosomal RNA and small nuclear RNA (snRNA) genes, is of great interest because of the relatively harmless nature, stable inheritance and possible application for targeted gene delivery of target-specific transposable elements. To date, such strict target specificity has been observed only among non-LTR retrotransposons. We here report a new superfamily of sequence-specific DNA transposons, designated Dada. Dada encodes a DDE-type transposase that shows a distant similarity to transposases encoded by eukaryotic MuDR, hAT, P and Kolobok transposons, as well as the prokaryotic IS256 insertion element. Dada generates 6-7 bp target site duplications upon insertion. One family of Dada DNA transposons targets a specific site inside the U6 snRNA genes and are found in various fish species, water flea, oyster and polycheate worm. Other target sequences of the Dada transposons are U1 snRNA genes and different tRNA genes. The targets are well conserved in multicopy genes, indicating that copy number and sequence conservation are the primary constraints on the target choice of Dada transposons. Dada also opens a new frontier for target-specific gene delivery application.
转座元件在多拷贝基因(如核糖体 RNA 和小核 RNA (snRNA) 基因)中的靶向整合非常有趣,因为其具有相对无害、稳定遗传和可能用于靶向基因传递的特性。迄今为止,这种严格的靶向特异性仅在非 LTR 反转录转座子中观察到。我们在这里报告了一个新的序列特异性 DNA 转座子超家族,命名为 Dada。Dada 编码一种 DDE 型转座酶,与真核 MuDR、hAT、P 和 Kolobok 转座子以及原核 IS256 插入元件编码的转座酶具有远缘相似性。Dada 在插入时产生 6-7 bp 的靶位点重复。一类 Dada DNA 转座子靶向 U6 snRNA 基因内部的特定位点,存在于各种鱼类、水蚤、牡蛎和多毛类蠕虫中。Dada 转座子的其他靶序列是 U1 snRNA 基因和不同的 tRNA 基因。这些靶序列在多拷贝基因中高度保守,表明拷贝数和序列保守性是 Dada 转座子靶选择的主要限制因素。Dada 还为靶向基因传递应用开辟了一个新的前沿。