生殖細胞負責遺傳信息的時代傳遞，那么基因組的完整性對于生殖細胞至關重要。而在真核生物精細胞中，有許多外來侵入的轉(zhuǎn)座子、逆轉(zhuǎn)座子等移動型遺傳元件。這些自私的遺傳元件在染色體不同位點間跳躍，造成基因突變和基因組損傷。在生殖細胞中，轉(zhuǎn)座子的跳躍可能會導致不育。PiRNA/Piwi能夠高效的阻止轉(zhuǎn)座子等元件對基因組的損傷。研究發(fā)現(xiàn)，piRNA起源于反轉(zhuǎn)座子、重復序列等區(qū)域，與Piwi蛋白形成piRNA/Piwi機器，沉默轉(zhuǎn)座子、反轉(zhuǎn)座子等。此外，piRNA還可以發(fā)揮類似于siRNA的功能，參與調(diào)控生殖細胞中編碼基因的表達。

方法：

研究人員發(fā)現(xiàn)無精子癥患者體內(nèi)Piwi（Hiwi）生殖突變會阻止其泛素化和降解。為了了解其中的作用機制，研究人員構建了Piwi（Miwi）突變敲入小鼠模型，證明了這種遺傳缺陷直接導致了男性不育癥。具體來說，研究人員發(fā)現(xiàn)MIWI能以一種對立于Piwi作用RNA（piRNA）的方式，與組蛋白泛素連接酶RNF8結合，并在晚期精子細胞的細胞質(zhì)中穩(wěn)定螯合RNF8，從而導致精子異常，引起組蛋白滯留，形態(tài)異常和活性嚴重受損，而這可以通過RNF8-N阻斷精子細胞中RNF8-MIWI的相互作用，逆轉(zhuǎn)功能。

研究人員篩查了413例臨床無精、弱精癥患者Piwi基因上控制Piwi蛋白泛素化修飾降解的關鍵元件D-box，發(fā)現(xiàn)有3例病人在此元件中存在雜合性基因突變，且發(fā)現(xiàn)此類突變可來源于基因自發(fā)突變，也可從母親遺傳獲得。為鑒定此類突變是否是造成這些患者發(fā)生無精/少弱精的原因，研究人員將其中的一組突變條件型敲入小鼠Piwi基因，在小鼠模型中研究此類突變對精子發(fā)生的作用。他們發(fā)現(xiàn)， Piwi D-box雜合突變小鼠均出現(xiàn)雄性不育，精子表型也與患者*。深入研究發(fā)現(xiàn)，Miwi D-box雜合突變小鼠精子發(fā)生阻滯在延長型精子細胞發(fā)育階段，盡管能產(chǎn)生少量精子，但精子形態(tài)異常、細胞核結構疏松、無活力。

機制研究揭示， PIWI蛋白具有將RNF8“扣留”于細胞核外的功能。正常小鼠體內(nèi)PIWI蛋白會在精子發(fā)育后期被自然降解，RNF8進入細胞核內(nèi)開啟“組蛋白-魚精蛋白轉(zhuǎn)換”，幫助精子發(fā)育完成。而Piwi蛋白突變導致其在后期不能被正常代謝，大量RNF8因此被“扣留”在細胞核外，魚精蛋白與組蛋白交換受阻，zui終造成精子發(fā)育受阻。將RNF8-N端導入突變小鼠的精子細胞后，可有效阻斷Piwi基因蛋白產(chǎn)物對RNF8的“扣留”，恢復精子的正常形態(tài)及游動能力，提示該策略對臨床治療此類無精、弱精癥具有重要理論參考價值。

According to foreign media reports, an international research team led by Dirk Schulze-Makuch, Washington State University, found that the most Spartan, seemingly lifeless place on the earth's surface is not so lifeless. Once considered or even lack of microbes, the Atacama Desert showed special bacteria reproduction after rainfall. This indicates that there may be similar "dormancy" groups on red planet.

Atacama Desert is thought to be the earth's closest natural environment to Mars. The living environment of the Chilean desert is so bad that even bacteria can not survive under normal conditions. The rainfall here is measured in millimeters per ten years. Although the 10 million - year history of the desert Mediterranean climate is surprising, there is not enough water to sustain life. Worse, cold temperatures mean less energy that can be used for growth and reproduction.

According to Schulze-Makuch, when the Washington State University's research began in 2015, the unanimate reputation seemed to be intact. Although they found some microbes and DNA traces in Atacama Desert, these residues were proved to come from the outside world.

When the desert first came to rain for decades, the situation changed. It activated the long time dormant biological groups buried under the surface. These groups made full use of a short chance to reproduce. When the research team returned in 2016 and 2017, they found that these populations were gradually dormant when the soil dried up. However, they obtained uncontaminated samples by using sterilized spoon and special instruments, and identified several kinds of local microbial species by genome analysis.

"In the past, researchers have found dead organisms and DNA residues near the surface, but this is the first discovery of persistent life forms in the soil of Atacama Desert," Schulze-Makuch said. "We believe that these microbial communities can be dormant for hundreds of years or even thousands of years on very similar conditions found on planets like Mars, and then return to life when it rains."

Schulze-Makuch believes that the impact on Mars research is quite large. Though the environment of Mars is so desolate now, billions of years ago, this place is a very different place. There are shallow seas, rivers and lakes, and simple living things have evolved. As Mars becomes colder and drier, it is possible to adapt to some forms of life by long dormancy.

"We know that the water in the Martian soil is frozen, and recent studies strongly show that the night rain and other increased humidity events near the surface," Schulze-Makuch said. "If life has evolved on Mars, our research shows that it may be alive under the dry surface of today."

The Washington State University's research team is scheduled to return to Atacama Desert in March 15th for another two weeks of investigation, which may involve the discovery of more microorganisms. "There are only a few places left on the planet to find new forms of life that can survive on that environment on Mars," Schulze-Makuch said. Our goal is to understand how they do this so that we know what to look for on the surface of Mars. "

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