A novel class of small RNAs bind to MILI protein in mouse testes

A novel class of small RNAs bind to MILI protein in mouse testes
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DOI:
10.1038/nature04916
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发表时间:
2006-07-13
期刊:
影响因子:
64.8
通讯作者:
Tuschl, Thomas
Tuschl, Thomas
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Aravin, Alexei;Gaidatzis, Dimos;Tuschl, Thomas

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与Argonaute蛋白结合的小RNA在不同的基因沉默过程中识别部分或完全互补的核酸靶标(1-4)。Argonaute蛋白的一个亚组-称为“Piwi家族”(5)-是无脊椎动物生殖细胞和干细胞发育所必需的(6,7),两个Piwi成员- MILI和MIWI -是小鼠精子发生所必需的(8,9)。在这里,我们描述了一类新的小RNA结合到小鼠雄性生殖细胞中的MILI,它们在减数分裂开始时积累。超过1,000种鉴定的独特分子的序列共享对50个尿苷的强烈偏好,但在其他方面不能容易地分类到序列家族中。这些小RNA的基因组作图揭示了有限数量的簇,表明这些RNA是从长初级转录物加工而来的。小RNA的长度为26 - 31个核苷酸(nt)-与microRNA(miRNAs)或短干扰RNA(siRNAs)的21 - 23 nt明显不同-我们将其称为“Piwi相互作用RNA”或piRNA。正交的人染色体区域也产生具有piRNA特征的小RNA,但克隆的序列是不同的。这类新的小RNA的鉴定为确定Piwi蛋白在哺乳动物精子发生中的分子功能提供了一个重要的起点。
Small RNAs bound to Argonaute proteins recognize partially or fully complementary nucleic acid targets in diverse gene-silencing processes(1-4). A subgroup of the Argonaute proteins - known as the 'Piwi family'(5) - is required for germ- and stem-cell development in invertebrates(6,7), and two Piwi members - MILI and MIWI - are essential for spermatogenesis in mouse(8,9). Here we describe a new class of small RNAs that bind to MILI in mouse male germ cells, where they accumulate at the onset of meiosis. The sequences of the over 1,000 identified unique molecules share a strong preference for a 50 uridine, but otherwise cannot be readily classified into sequence families. Genomic mapping of these small RNAs reveals a limited number of clusters, suggesting that these RNAs are processed from long primary transcripts. The small RNAs are 26 - 31 nucleotides (nt) in length - clearly distinct from the 21 - 23 nt of microRNAs ( miRNAs) or short interfering RNAs (siRNAs) - and we refer to them as 'Piwi-interacting RNAs' or piRNAs. Orthologous human chromosomal regions also give rise to small RNAs with the characteristics of piRNAs, but the cloned sequences are distinct. The identification of this new class of small RNAs provides an important starting point to determine the molecular function of Piwi proteins in mammalian spermatogenesis.