The τCstF-64 polyadenylation protein controls genome expression in testis.

The τCstF-64 polyadenylation protein controls genome expression in testis.
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DOI:
10.1371/journal.pone.0048373
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
MacDonald CC
MacDonald CC
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li W;Yeh HJ;Shankarling GS;Ji Z;Tian B;MacDonald CC

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τCstF-64多聚腺苷酸化蛋白(基因符号Cstf 2 t)是CstF-64的睾丸表达直向同源物。敲除Cstf 2 t的小鼠具有仅在减数分裂和减数分裂后雄性生殖细胞中检测到的表型,这使我们有机会在分离的发育系统中检查CstF-64的功能。我们对野生型和Cstf 2 t −/−小鼠睾丸的cDNA进行了大规模平行克隆扩增测序。这些结果表明,τCstF-64的缺失导致基因组表达模式的大规模变化。我们确定Cstf 2 t −/−小鼠睾丸中内含子和基因间区域的RNA显著过量,并且伴随使用更远的多聚腺苷酸化位点。我们观察到这种效应,特别是在无内含子的小基因中,其中许多是表达的逆转录子,可能与τCstF-64共同进化。最后,我们观察到Cstf 2 t −/−睾丸中长散布核元件(LINE)序列的过度表达。这些结果表明,τCstF-64在生殖细胞表达基因的3′端决定和转录终止中起重要作用。
The τCstF-64 polyadenylation protein (gene symbol Cstf2t) is a testis-expressed orthologue of CstF-64. Mice in which Cstf2t was knocked out had a phenotype that was only detected in meiotic and postmeiotic male germ cells, giving us the opportunity to examine CstF-64 function in an isolated developmental system. We performed massively parallel clonally amplified sequencing of cDNAs from testes of wild type and Cstf2t−/− mice. These results revealed that loss of τCstF-64 resulted in large-scale changes in patterns of genome expression. We determined that there was a significant overrepresentation of RNAs from introns and intergenic regions in testes of Cstf2t−/− mice, and a concomitant use of more distal polyadenylation sites. We observed this effect particularly in intronless small genes, many of which are expressed retroposons that likely co-evolved with τCstF-64. Finally, we observed overexpression of long interspersed nuclear element (LINE) sequences in Cstf2t−/− testes. These results suggest that τCstF-64 plays a role in 3′ end determination and transcription termination for a large range of germ cell-expressed genes.
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