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1、單擊此處編輯母版標(biāo)題樣式,,單擊此處編輯母版文本樣式,,第二級(jí),,第三級(jí),,第四級(jí),,第五級(jí),,,*,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 黃玲艷,1

2、0112213119,小分子,RNAs,在配子形成發(fā)育、受精和早期合子發(fā)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.,,,,部分順式、反式小分子,RNAs,是目前被認(rèn)為有廣泛調(diào)節(jié)作用的可信調(diào)節(jié)基因，它參與了配子形成發(fā)育、受精、卵前期發(fā)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.,,,,這些小分子,RNAs,不僅在配子合子中具有維持基因完整性的功能，也具有活躍參與姐妹染色單體片段交換，還通過(guò)核質(zhì)影響受精卵形態(tài)發(fā)育。,,wikipedia,,微,RNA,（,microRNAs,；,miRNA,，又譯,小分子,RNA,）是真核生物中廣泛存在的一種長(zhǎng)約,21,到,23,個(gè),核苷酸,的,RNA,分子，可調(diào)節(jié)其他,基因,的,表達(dá),。,miRNA,來(lái)自一些從,DNA,轉(zhuǎn)錄,而來(lái)，但無(wú)法進(jìn)一步,轉(zhuǎn)譯,成,蛋白質(zhì),的,

5、RNA,（屬于,非編碼,RNA,）。,miRNA,通過(guò)與靶,信使核糖核酸,(mRNA),特異結(jié)合，從而抑制,轉(zhuǎn)錄,后,基因表達(dá),,,在調(diào)控基因表達(dá)、,細(xì)胞周期,、生物體發(fā)育時(shí)序等方面起重要作用。在動(dòng)物中，一個(gè)微,RNA,通?？梢哉{(diào)控?cái)?shù)十個(gè)基因,.,,,1989,年，,Victor,發(fā)現(xiàn),線(xiàn)蟲(chóng),,( C. elegans),中有個(gè),基因,,lin-4,抑制另一個(gè)基因,lin-14.,他們認(rèn)為,lin-4,應(yīng)該也表達(dá)一種調(diào)控,蛋白質(zhì),，因?yàn)榛蜣D(zhuǎn)錄成,RNA,并翻譯成蛋白質(zhì)是當(dāng)時(shí)認(rèn)為的公理。,1993,年，,Victor,的學(xué)生,Rosalind Lee,和,Phonda Feinbaum,克隆出

6、了,lin-4,，卻發(fā)現(xiàn)這個(gè)基因非常小，而且這個(gè)基因的產(chǎn)物不是蛋白質(zhì)，而是一個(gè)長(zhǎng)度只有,22,個(gè)核苷酸的,RNA,。它是由單鏈的,RNA,分子產(chǎn)生，這個(gè)分子的一端折回來(lái)形成不完全的互補(bǔ)配對(duì)，稱(chēng),",發(fā)卡結(jié)構(gòu),".,,,,activities,,1.Introduction to what is epigenetics(,實(shí)驗(yàn)胚胎學(xué),),,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.,,,保護(hù)精子和卵母細(xì)胞在受精過(guò)程中互配性,,,Silencing small RNAs,，,fall into three categories and how it works.,,,沉默,RNAs,分為三類(lèi)及它們各是如何作用的,,,,During preparati,on,,,small-RNA,–based mechanisms m,on,itor,and,enforce gametic genome integrity, which is required for successful,fertilizat

8、ion,.,,在準(zhǔn)備期，小分子,RNAs,為基礎(chǔ)的機(jī)制監(jiān)控和促使果蠅配偶子基因完整，這是成功繁殖的前提。,,,the female germline itself, composed of the haploid oocyte,and,polyploid nurse cells, faces the threat of many endogenous transpos,on,types.,→,Small-RNAs,,雌種系本身由雙倍體卵母細(xì)胞和多倍體培育細(xì)胞組成，面臨著許多內(nèi)生的轉(zhuǎn)座子的脅迫，,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：調(diào)控基因表達(dá)，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,).,,這個(gè)系統(tǒng)（理論上，母系,piRNA,可以容納無(wú)限數(shù)量的匹配轉(zhuǎn)座子,RNAs,）失敗了，然而，如果部分轉(zhuǎn)座子是序列太發(fā)散而不能被,piRNA,辨認(rèn)，這會(huì)導(dǎo)致“混合發(fā)育不完全”，轉(zhuǎn)座子侵入正在發(fā)育的受精卵基因引起基因不穩(wěn)定，而且，在后代不育,。,,transpos,on,轉(zhuǎn)座元件,（,英語(yǔ),：,Transposable element,，亦稱(chēng)為,轉(zhuǎn)座子,）是一類(lèi),DNA,序列，它們能夠在,基因組,中通過(guò),轉(zhuǎn)錄,或

12、,錄,，在,內(nèi)切酶,（,Nuclease,）的作用下，在其他,基因座,上出現(xiàn)。轉(zhuǎn)座子的這種行為，與,假基因,（,Pseudogene,）的出現(xiàn)頗有相似甚至相同之處。有些科學(xué)家將后者視為“基因化石”，是透視物種,進(jìn)化,的痕跡之一,[1],。轉(zhuǎn)座子的發(fā)現(xiàn)，證明了,基因組,并不是一個(gè)靜態(tài)的集合，而是一個(gè)不斷在改變自身構(gòu)成的動(dòng)態(tài)有機(jī)體。根據(jù)轉(zhuǎn)座子“跳躍”方式的不同，轉(zhuǎn)座子被分為,I,型和,II,型轉(zhuǎn)座子。,,,,,The kangaroo,,袋鼠,Brassica,,蕓薹,Drosophila,,果蠅,Arabidopsis,,擬南芥,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.,哺乳動(dòng)物機(jī)理類(lèi)似果蠅的，也類(lèi)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,在細(xì)胞和核細(xì)胞之間跨越也許代表了廣泛使用的配子或合子基因組的完整性和混合型。,,,,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,在一方和它們的目標(biāo)在其他地方對(duì)數(shù)期可以影響混合相容性。,,,Excessive phylogenetic distance between the two parents would, this way, be str,on,gly counterselected.,,,兩個(gè)親本間過(guò)大的系統(tǒng)發(fā)育距離，會(huì)被強(qiáng)制篩選。,,,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.,,,因此有力證實(shí)環(huán)境因素在親本不僅能影響后代，也能影響把基因傳給后代的能力。,,,,All in all,,Small-RNA,↙,↘,↓,Gametogenesis,Fertilization,EarlyZygotic Development,,Important!,Thank you !,,