Mishima Yuichiro, Giraldez Antonio J, Takeda Yasuaki, Fujiwara Toshinobu, Sakamoto Hiroshi, Schier Alexander F, Inoue Kunio
Department of Biology, Graduate School of Science and Technology, Kobe University, 1-1 Rokkodaicho, Nadaku, Kobe 657-8501, Japan.
Curr Biol. 2006 Nov 7;16(21):2135-42. doi: 10.1016/j.cub.2006.08.086.
Early in development, primordial germ cells (PGCs) are set aside from somatic cells and acquire a unique gene-expression program . The mechanisms underlying germline-specific gene expression are largely unknown. Nanos expression is required during germline development and is posttranscriptionally restricted to PGCs . Here we report that the microRNA miR-430 targets the 3' untranslated region (UTR) of nanos1 during zebrafish embryogenesis. A miR-430 target site within the nanos1 3' UTR reduces poly(A) tail length, mRNA stability, and translation. Repression is disrupted in maternal-zygotic dicer mutants (MZdicer), which lack mature miRNAs , and is restored by injection of processed miR-430. Although miR-430 represses other genes equally in germline and soma, specific regions in the nanos1 3' UTR compensate for microRNA-mediated repression in PGCs and allow germline-specific expression. We show that the 3' UTR of an additional PGC-specific gene, TDRD7, is also targeted by miR-430. These results indicate that miR-430 targets the 3' UTRs of germline genes and suggest that differential susceptibility to microRNAs contributes to tissue-specific gene expression.
在发育早期，原始生殖细胞（PGCs）从体细胞中分离出来，并获得独特的基因表达程序。生殖系特异性基因表达的潜在机制在很大程度上尚不清楚。Nanos表达在生殖系发育过程中是必需的，并且在转录后仅限于PGCs。在这里，我们报道了在斑马鱼胚胎发生过程中，微小RNA miR-430靶向nanos1的3'非翻译区（UTR）。nanos1 3'UTR内的一个miR-430靶位点会缩短多聚腺苷酸（poly(A)）尾巴长度、降低mRNA稳定性并抑制翻译。在缺乏成熟miRNA的母源合子双切酶突变体（MZdicer）中，这种抑制作用被破坏，而通过注射加工后的miR-430可以恢复。虽然miR-430在生殖系和体细胞中对其他基因的抑制作用相同，但nanos1 3'UTR中的特定区域可补偿PGCs中微小RNA介导的抑制作用，并允许生殖系特异性表达。我们发现另一个PGC特异性基因TDRD7的3'UTR也被miR-430靶向。这些结果表明，miR-430靶向生殖系基因的3'UTR，并提示对微小RNA的不同敏感性有助于组织特异性基因表达。
