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1、单击此处编辑母版标题样式,,单击此处编辑母版文本样式,,第二级,,第三级,,第四级,,第五级,,,*,A Small-RNA Perspective on Gametogenesis, Fertilization, and Early Zygotic Development,,Science 29 October 2010:,France. Institut Curie,,Institut de Biologie Moléculaire des Plantes,,Switzerl,and,.,,Swiss Federal Institute of Technology,10,生技 黄玲艳,1

2、0112213119,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 populati,on,s of cis-,and,trans-acting small RNAs have recently emerged as key regulators of extensive epigenetic changes taking place during,,peric,on,cepti,on,, which encompasses,gametogenesis,,,fertilization,,,and,,early,,zygotic,de

3、velopment.,,,,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,on,ly important to maintain genome integrity in the gametes,and,zygote, but they also actively c,on,tribute to assessing the compatibility of parental genomes at,fertilization,,and,to promoti

4、ng l,on,g-,term,memory of the,zygotic,epigenetic l,and,scape 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,

5、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.,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

6、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.Preparation,,3.Confrontation,,4.Consolidation,,5.Hybird incompatibilities(,混合不兼容,),,,,,Protecting the sperm,and,oocyte, assessin

7、g 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 preparati,on,,,small-RNA,–based mechanisms m,on,itor,and,enforce gametic genome integrity, which is required for successful,fertilizat

8、ion,.,,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 transpos,on,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 the embryo, these paternal

9、 21-nt siRNAs could degrade,（降低）,transpos,on,RNAs that have potentially escaped TGS,,,,This process could, in principle, unfavorably silence master ping-p,on,g piRNA clusters (e.g., 42AB),and,ultimately compromise the pathway’s adaptive potential, but a distinct HP1 homolog, Rhino, apparently preven

10、ts this by competing with HP1α at the 42AB locus,,即：调控基因表达，形成,what,,,,The system fails, however, if paternal transpos,on,s are too sequence-divergent to be recognized by the maternal piRNA reservoir (,Fig. 4A,). This incurs “hybrid dysgenesis,” where transpos,on,s invading the developing embry,on,ic

11、 germline cause 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,。,,transpos,on,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

12、,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,（,Pseudogene,）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

13、germline produces amplifiable piRNAs (,32,),,and,similarly to plants, genome-wide demethylati,on,unmasks transpos,on,s (,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 mig

14、ht thus represent widely used mechanisms for gametic or,zygotic,genome integrity,and,hybrid compatibility.,,,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。,,,,Expressi,on,or sequence polymorphisms between regulatory small RNAs in,on,e parent,and,their targets in the other could also influence hybrid com

15、patibility during the c,on,fr,on,tati,on,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 between the two parents would, this way, be str,on,gly counterselected.,,,两个亲本间过大的系统发育距离，会被强制筛选。,,,It is thus c,on,ceivable that envir,on,mental cues perceived in parents might not,on,ly affect epigenetic transgenerati,on,al memory (,43,), but also the mere capacity to pass their genome to subsequent generati,on,s.,,,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 !,,