Role of gonadotropin regulated testicular RNA helicase (GRTH/Ddx25) on polysomal associated mRNAs in mouse testis.
Role of gonadotropin regulated testicular RNA helicase (GRTH/Ddx25) on polysomal associated mRNAs in mouse testis.
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DOI：
10.1371/journal.pone.0032470
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Dufau ML
中科院分区：
文献类型：
--
作者：
Tsai-Morris CH;Sato H;Gutti R;Dufau ML
促性腺激素调节的睾丸RNA解旋酶（GRTH/Ddx 25）是一种睾丸特异性多功能RNA解旋酶，是精子发生的重要转录后调节因子。GRTH将相关mRNA从减数分裂和单倍体生殖细胞的细胞核转运到细胞质位点，并与主动翻译的多核糖体相关。它也是Leydig细胞中类固醇生成的负调节剂。为了获得GRTH调节基因的全基因组视角，特别是与多聚核糖体相关的基因，使用从野生型（WT）和GRTH KO小鼠睾丸分离的多聚核糖体结合的RNA进行微阵列差异基因表达分析。在WT小鼠基因组中发现792个基因与多聚体GRTH连锁。其中186个基因在GRTH基因敲除小鼠中表达下调，7个基因表达上调。使用从纯化的生殖细胞群提取的总RNA进行类似的分析，以解决单个靶细胞中的GRTH作用。在GRTH KO的多聚体位点与精子发生相关的已知基因的下调及其与WT中GRTH的相关性，加上早期发现的少量或不变的总mRNA及其在KO中蛋白表达的消除，强调了GRTH在翻译中的相关性。免疫抑制途径分析预测GRTH结合多核糖体基因与泛素-蛋白酶体-热休克蛋白信号网络途径相关，差异表达基因分析推导出NFκB B/TP 53/TGFB 1信号网络。这项研究揭示了男性生殖中GRTH作用的基因组和调控途径中已知和未探索的因素。
Gonadotropin Regulated Testicular RNA Helicase (GRTH/Ddx25) is a testis-specific multifunctional RNA helicase and an essential post-transcriptional regulator of spermatogenesis. GRTH transports relevant mRNAs from nucleus to cytoplasmic sites of meiotic and haploid germ cells and associates with actively translating polyribosomes. It is also a negative regulator of steroidogenesis in Leydig cells. To obtain a genome-wide perspective of GRTH regulated genes, in particularly those associated with polyribosomes, microarray differential gene expression analysis was performed using polysome-bound RNA isolated from testes of wild type (WT) and GRTH KO mice. 792 genes among the entire mouse genome were found to be polysomal GRTH-linked in WT. Among these 186 were down-regulated and 7 up-regulated genes in GRTH null mice. A similar analysis was performed using total RNA extracted from purified germ cell populations to address GRTH action in individual target cells. The down-regulation of known genes concerned with spermatogenesis at polysomal sites in GRTH KO and their association with GRTH in WT coupled with early findings of minor or unchanged total mRNAs and abolition of their protein expression in KO underscore the relevance of GRTH in translation. Ingenuity pathway analysis predicted association of GRTH bound polysome genes with the ubiquitin-proteasome-heat shock protein signaling network pathway and NFκB/TP53/TGFB1 signaling networks were derived from the differentially expressed gene analysis. This study has revealed known and unexplored factors in the genome and regulatory pathways underlying GRTH action in male reproduction.
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