The nuclear RNA-binding protein Sam68 translocates to the cytoplasm and associates with the polysomes in mouse spermatocytes
The nuclear RNA-binding protein Sam68 translocates to the cytoplasm and associates with the polysomes in mouse spermatocytes
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DOI：
10.1091/mbc.e05-06-0548
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发表时间：
2006-01-01
影响因子：
3.3
通讯作者：
Sette, C
中科院分区：
文献类型：
--
作者：
Paronetto, MP;Zalfa, F;Sette, C
翻译控制在蠕虫和哺乳动物等不同生物的配子发生过程中起着至关重要的作用。小鼠基因敲除模型已经强调了许多RNA结合蛋白在精子发生过程中的重要功能。在此，我们研究了哺乳动物雄性减数分裂过程中Sam 68的表达和功能，Sam 68是一种RNA结合蛋白，参与RNA代谢的几个方面。Sam 68在细胞内的表达和定位是阶段特异性的：它在精原细胞的细胞核中表达，在减数分裂开始时（细线期/偶线期阶段）消失，并且它再次在粗线期精母细胞和圆形精子细胞的细胞核中积累。在减数分裂期间，Sam 68易位到细胞质中，在那里它被发现与多核糖体结合。易位与丝氨酸/苏氨酸磷酸化相关，并被促分裂原活化蛋白激酶ERK 1/2和成熟促进因子cyclinB-cdc 2复合物的抑制剂阻断。这两种激酶都与粗线期精母细胞中的Sam 68相关，并磷酸化Sam 68 RNA结合基序上游和下游的调控区。小鼠精母细胞中与Sam 68相关的mRNA的分子克隆揭示了在精子发生过程中可能由这种RNA结合蛋白进行转录后调节的基因子集。我们还证明，Sam 68穿梭于细胞核和细胞质之间的次级精母细胞，这表明它可能促进特定的RNA靶在减数分裂分裂期间的翻译。
Translational control plays a crucial role during gametogenesis in organisms as different as worms and mammals. Mouse knockout models have highlighted the essential function of many RNA-binding proteins during spermatogenesis. Herein we have investigated the expression and function during mammalian male meiosis of Sam68, an RNA-binding protein implicated in several aspects of RNA metabolism. Sam68 expression and localization within the cells is stage specific: it is expressed in the nucleus of spermatogonia, it disappears at the onset of meiosis (leptotene/zygotene stages), and it accumulates again in the nucleus of pachytene spermatocytes and round spermatids. During the meiotic divisions, Sam68 translocates to the cytoplasm where it is found associated with the polysomes. Translocation correlates with serine/ threonine phosphorylation and it is blocked by inhibitors of the mitogen activated protein kinases ERK1/2 and of the maturation promoting factor cyclinB-cdc2 complex. Both kinases associate with Sam68 in pachytene spermatocytes and phosphorylate the regulatory regions upstream and downstream of the Sam68 RNA-binding motif. Molecular cloning of the mRNAs associated with Sam68 in mouse spermatocytes reveals a subset of genes that might be posttranscriptionally regulated by this RNA-binding protein during spermatogenesis. We also demonstrate that Sam68 shuttles between the nucleus and the cytoplasm in secondary spermatocytes, suggesting that it may promote translation of specific RNA targets during the meiotic divisions.