piRNA生物学起源及功能研究进展

piRNA属于非编码小RNA的一员,常见于生殖系干细胞中.既往学者们认为它主要在维持干细胞功能、配子的形成以及沉默外来转座子等方面发挥作用.但近来在体细胞系中的发现,使得人们对它的生物起源以及功能行使有了更大的兴趣.就piRNA的发现、结构特征、功能与基因调控等进行了综述.     

PIWI/piRNA“机器”与雄性生殖细胞发育

PIWI(P-element-induced wimpy testis)蛋白在动物生殖系细胞中特异性表达,为动物生殖细胞发育分化所必需。piRNA(PIWI-interacting RNAs)是最近在动物生殖系细胞中发现的一类非编码小分子RNA,这类小RNA特异性地与PIWI家族蛋白相互作用。PIWI/piRNA"机器"通过沉默转座元件和调控编码mRNA等方式在动物生殖细胞发育分化过程中发挥重要作用。本文围绕PIWI/piRNA"机器"的生物学功能及分子机制,对近期取得的相关研究进展进行了系统性总结。     

piRNA/PIWI功能调控与精子发生

piRNAs(PIWI-interacting RNAs)是一类与PIWI相互作用的小非编码RNAs(small noncoding RNAs, sncRNAs),其长度介于24~32 nt,特异性地在动物生殖腺细胞中表达。近来研究表明piRNA/PIWI系统在动物生殖腺细胞的基因组转座元件沉默及转录后调控mRNAs方面具有重要功能。最近,中国科学院上海生物化学与细胞生物学研究所刘默芳课题组的一项研究表明,在人和小鼠的精子发生过程中,PIWI (鼠源同源蛋白MIWI、人源同源蛋白HIWI)的严格代谢调控至关重要。以此为契机,本文综述了piRNA/PIWI在哺乳动物(主要是小鼠和人)精子发生过程中调控功能的研究进展。     

piRNA通路在哺乳动物雌性生殖中具有不可或缺的功能

piRNA是一类非编码小RNA,它在生殖细胞中针对基因组行使免疫系统的功能,抑制转座元件,维持基因组的稳定性.已有的研究表明,piRNA在模式动物果蝇和斑马鱼的两性生殖,以及小鼠的雄性生殖中都是必需的,但对小鼠的雌性生殖却是非必需的,因此形成了piRNA对哺乳动物的雌性生殖不重要的默认共识.该团队通过建立单细胞小R...     

piRNA的功能研究进展

piRNA是一类种类繁多的小RNA,通常在生殖类细胞中表达,其功能是抑制转座子的转座,维持基因组结构的稳定性。对线虫piRNA研究发现,piRNA还具有记忆基因表达的功能。体细胞和癌细胞中piRNA的发现,更凸显了piRNA功能的重要性和多样性。本文梳理了近几年来piRNA功能研究的最新成果,包括piRNA在调控转座子、mRNA、lncRNA、DNA甲基化修饰、染色体表观修饰等方面的功能,同时也探讨了piRNA和癌症的关系。     

piRNA——一种新型的小分子RNA

小分子RNA已成为全球生物学研究关注的热点之一.最近,在哺乳动物的生殖细胞中发现了一种新型的小分子RNA：piRNA,比以往发现的小分子RNA稍长些,大小在30个核苷酸左右,piRNA必须与哺乳动物的Piwi蛋白结合才能发挥作用.目前对piRNA的研究还处于初始阶段,但鉴于piRNA主要分布在包括人类等数种动物体睾丸的精原细胞内,科学家们推测这类小分子RNA可能与动物体内精子的发育和维持的功能相关.     

组蛋白修饰在卵母细胞发育中功能和调控机制的研究进展

组蛋白修饰作为表观遗传调控网络的重要组成部分,其主要的修饰类型包括乙酰化、甲基化、磷酸化等,在卵母细胞减数分裂过程中呈现动态变化.在卵母细胞发育过程中,表观遗传调控因子涉及的乙酰化、甲基化维持、磷酸化和组蛋白置换调控着卵母细胞减数分裂过程中基因的表达、纺锤体的组装、染色体的排列和基因组的稳定性,确保了卵母细胞减数分裂的...     

植物PHD结构域蛋白的结构与功能特性

植物同源结构域(plant homeodomain,PHD)是锌指结构域家族的一类转录调控因子,其最主要的功能是可以识别各种组蛋白修饰密码,包括组蛋白甲基化和乙酰化等;此外PHD结构域还可以与DNA结合.含有PHD结构域的蛋白,或者本身具有组蛋白修饰酶活性,或者可以与各类组蛋白修饰酶相互作用,还有部分与DNA甲基化相关...     

精子发生转录调控机制的研究进展

精子发生过程中的转录调控是由一系列基因表达和调控事件组成的复杂过程,影响精子的形成、质量和功能。转录调控过程介导与精子形成密切相关的基因,包括精子特异性基因、组蛋白基因和其他转录因子的基因表达。这些基因的表达和沉默受到转录因子、表观遗传修饰和非编码RNA等多种机制的调控。此外,转录调控在精子发生的不同阶段起着不同的作用,包括精原干细胞的自我更新和分化、精母细胞的减数分裂和精子细胞的变形成熟。深入理解精子发生中的转录调控机制对于研究精子形成的生物学过程、解析生育障碍的病理机制以及开发生育问题相关的治疗方法具有重要的意义。     

piRNA的生物学功能

非编码小RNA（non-coding RNA, ncRNA）主要有siRNA（small interfering RNA）、miRNA(microRNA)和piRNA (piwi-interacting RNA)三类,其中piRNA是近年来新发现的一类小RNA分子,特异性地同Argonuat蛋白家族中的Piwi亚家族蛋白结合,主要在生殖细胞系中表达,对维持生殖系DNA完整、抑制转座子转录、抑制翻译、参与异染色质的形成、执行表观遗传调控和生殖细胞发生等均有重要作用．piRNA基因几乎遍布于整个基因组,但呈高度不连续性分布,大部分定位于20～90 kb的染色体基因簇上．与来自于双链RNA的siRNA和发卡结构miRNA不同之处是piRNA来自长单链RNA前体,或者是两股非重叠的反向转录前体,其生成与Dicer无关．作为调节RNA（riboregulator）,piRNA和miRNA可能在动物起源早期就已经出现了,帮助生命进入了一个多细胞动物的时代,产生了今天的生物体复杂性和多样性．piRNA成为ncRNA的研究热点,进展飞快,有很多综述及时介绍piRNA的研究进展,本文结合siRNA、miRNA的特点介绍了关于piRNA的形成机制和作用的最新研究成果．     

The regulatory function of piRNA/PIWI complex in cancer and other human diseases: The role of DNA methylation

Piwi-interacting RNAs (piRNAs) are a class of short chain noncoding RNAs that are constituted by 26-30 nucleotides (nt) and can couple with PIWI protein family. piRNAs were initially described in germline cells and are believed to be critical regulators of the maintenance of reproductive line. Increasing evidence has extended our perspectives on the biological significance of piRNAs and indicated that they could still affect somatic gene expression through DNA methylation, chromatin modification and transposon silencing, etc. Many studies have revealed that the dysregulation of piRNAs might contribute to diverse diseases through epigenetic changes represented by DNA methylation and chromatin modification. In this review, we summarized piRNA/PIWI protein-mediated DNA methylation regulation mechanisms and methylation changes caused by piRNA/PIWI proteins in different diseases, especially cancers. Since DNA methylation and inhibitory chromatin marks represented by histone H3 lysine 9 (H3K9) methylation frequently cooperate to silence genomic regions, we also included methylation in chromatin modification within this discussion. Furthermore, we discussed the potential clinical applications of piRNAs as a new type promising biomarkers for cancer diagnosis, as well as the significance of piRNA/PIWI protein-associated methylation changes in treatment, providing disparate insights into the potential applications of them.     

Mouse primordial germ-cell-like cells lack piRNAs

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Biological significance of piRNA in liver cancer: a review

Abstract

Liver cancer is one of the most common and deadly cancers in the world. In recent years, non-coding RNA has been a hot topic in liver cancer research. piRNAs (PIWI-interacting RNAs) are a new type of small non-coding RNA, which are formed by the PIWI proteins interacting with RNA. The latest research shows that piRNA and PIWI proteins are abnormally expressed in various cancers, including pancreatic, colorectal, breast, etc. piRNA plays an important regulatory role in liver cancer. In this review, we discuss the biological function of piRNAs and new progress in the development of liver cancer, and new targets and ideas for piRNA and PIWI proteins in the diagnosis and treatment of liver cancer.     

Functional involvement of Tudor and dPRMT5 in the piRNA processing pathway in Drosophila germlines

In Drosophila, the PIWI proteins, Aubergine (Aub), AGO3, and Piwi are expressed in germlines and function in silencing transposons by associating with PIWI‐interacting RNAs (piRNAs). Recent studies show that PIWI proteins contain symmetric dimethyl‐arginines (sDMAs) and that dPRMT5/Capsuleen/DART5 is the modifying enzyme. Here, we show that Tudor (Tud), one of Tud domain‐containing proteins, associates with Aub and AGO3, specifically through their sDMA modifications and that these three proteins form heteromeric complexes. piRNA precursor‐like molecules are detected in these complexes. The expression levels of Aub and AGO3, along with their degree of sDMA modification, were not changed by tud mutations. However, the population of transposon‐derived piRNAs associated with Aub and AGO3 was altered by tud mutations, whereas the total amounts of small RNAs on Aub and AGO3 was increased. Loss of dprmt5 did not change the stability of Aub, but impaired its association with Tud and lowered piRNA association with Aub. Thus, in germline cells, piRNAs are quality‐controlled by dPRMT5 that modifies PIWI proteins, in tight association with Tud.