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1、A Small-RNA Perspective on Gametogenesis,Fertilization,and Early Zygotic Development,Science 29 October 2010:France.Institut CurieInstitut de Biologie Molculaire des PlantesSwitzerland.Swiss Federal Institute of Technology,10生技 黄玲艳,小分子RNAs在配子形成发育、受精和早期合子发育中的作用。,Abstract,Transient populations of cis-
2、and trans-acting small RNAs have recently emerged as key regulators of extensive epigenetic changes taking place during periconception,which encompasses gametogenesis,fertilization,and early zygotic development.部分顺式、反式小分子RNAs是目前被认为有广泛调节作用的可信调节基因，它参与了配子形成发育、受精、卵前期发育。,Abstract,These small RNAs are not
3、 only important to maintain genome integrity in the gametes and zygote,but they also actively contribute to assessing the compatibility of parental genomes at fertilization and to promoting long-term memory of the zygotic epigenetic landscape by affecting chromatin.这些小分子RNAs不仅在配子合子中具有维持基因完整性的功能，也具有活
4、跃参与姐妹染色单体片段交换，还通过核质影响受精卵形态发育。,wikipedia,微RNA（microRNAs；miRNA，又译小分子RNA）是真核生物中广泛存在的一种长约21到23个核苷酸的RNA分子，可调节其他基因的表达。miRNA来自一些从DNA转录而来，但无法进一步转译成蛋白质的RNA（属于非编码RNA）。miRNA通过与靶信使核糖核酸(mRNA)特异结合，从而抑制转录后基因表达,在调控基因表达、细胞周期、生物体发育时序等方面起重要作用。在动物中，一个微RNA通常可以调控数十个基因.1989年，Victor发现线虫(C.elegans)中有个基因 lin-4 抑制另一个基因 lin-14
5、.他们认为 lin-4 应该也表达一种调控蛋白质，因为基因转录成RNA并翻译成蛋白质是当时认为的公理。1993年，Victor的学生 Rosalind Lee 和 Phonda Feinbaum 克隆出了 lin-4，却发现这个基因非常小，而且这个基因的产物不是蛋白质，而是一个长度只有22个核苷酸的RNA。它是由单链的RNA分子产生，这个分子的一端折回来形成不完全的互补配对，称发卡结构.,activities,1.Introduction to what is epigenetics(实验胚胎学)2.Preparation3.Confrontation4.Consolidation5.Hybi
6、rd incompatibilities(混合不兼容),Protecting the sperm and oocyte,assessing their compatibility at fertilization.保护精子和卵母细胞在受精过程中互配性 Silencing small RNAs，fall into three categories and how it works.沉默RNAs分为三类及它们各是如何作用的,During preparation,small-RNAbased mechanisms monitor and enforce gametic genome integrit
7、y,which is required for successful fertilization.在准备期，小分子RNAs为基础的机制监控和促使果蝇配偶子基因完整，这是成功繁殖的前提。the female germline itself,composed of the haploid oocyte and polyploid nurse cells,faces the threat of many endogenous transposon types.Small-RNAs 雌种系本身由双倍体卵母细胞和多倍体培育细胞组成，面临着许多内生的转座子的胁迫，so，Small-RNAs作用,In th
8、e embryo,these paternal 21-nt siRNAs could degrade（降低）transposon RNAs that have potentially escaped TGS,This process could,in principle,unfavorably silence master ping-pong piRNA clusters(e.g.,42AB)and ultimately compromise the pathways adaptive potential,but a distinct HP1 homolog,Rhino,apparently
9、prevents this by competing with HP1 at the 42AB locus 即：调控基因表达，形成what,The system fails,however,if paternal transposons are too sequence-divergent to be recognized by the maternal piRNA reservoir(Fig.4A).This incurs“hybrid dysgenesis,”where transposons invading the developing embryonic germline cause
10、 genome instability and,ultimately,sterility in the offspring(22,29).这个系统（理论上，母系piRNA可以容纳无限数量的匹配转座子RNAs）失败了，然而，如果部分转座子是序列太发散而不能被piRNA辨认，这会导致“混合发育不完全”，转座子侵入正在发育的受精卵基因引起基因不稳定，而且，在后代不育。,transposon,转座元件（英语：Transposable element，亦称为转座子）是一类DNA序列，它们能够在基因组中通过转录或录，在内切酶（Nuclease）的作用下，在其他基因座上出现。转座子的这种行为，与假基因（Ps
11、eudogene）的出现颇有相似甚至相同之处。有些科学家将后者视为“基因化石”，是透视物种进化的痕迹之一1。转座子的发现，证明了基因组并不是一个静态的集合，而是一个不断在改变自身构成的动态有机体。根据转座子“跳跃”方式的不同，转座子被分为I型和II型转座子。,The kangaroo袋鼠,Brassica芸薹,Drosophila果蝇,Arabidopsis拟南芥,As in Drosophila,the mammalian germline produces amplifiable piRNAs(32),and similarly to plants,genome-wide demethyl
12、ation unmasks transposons(33),although mammalian gametes do not rely on accessory or nursing cells for this.,哺乳动物机理类似果蝇的，也类似于植物的。,Conclusions and Perspectives,RNA cross talk between nuclei or cells might thus represent widely used mechanisms for gametic or zygotic genome integrity and hybrid compati
13、bility.RNA在细胞和核细胞之间跨越也许代表了广泛使用的配子或合子基因组的完整性和混合型。Expression or sequence polymorphisms between regulatory small RNAs in one parent and their targets in the other could also influence hybrid compatibility during the confrontation phase.小分子RNAs在一方和它们的目标在其他地方对数期可以影响混合相容性。,Excessive phylogenetic distance
14、between the two parents would,this way,be strongly counterselected.两个亲本间过大的系统发育距离，会被强制筛选。It is thus conceivable that environmental cues perceived in parents might not only affect epigenetic transgenerational memory(43),but also the mere capacity to pass their genome to subsequent generations.因此有力证实环境因素在亲本不仅能影响后代，也能影响把基因传给后代的能力。,All in all,Small-RNA,Gametogenesis,Fertilization,EarlyZygotic Development,Important!,Thank you!,
