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选择性剪接的调节通过激活子和抑制子实现 The regulating sequences : exonic (or intronic) splicing enhancers (ESE or ISE) or silencers (ESS and ISS). The former enhance and the latter repress splicing. Proteins that regulate splicing bind to these specific sites for their action SR proteins binding to enhancers act as activators. (1) One domain is the RNA-recognition motif (RRM) (2) The other domain is RS domain rich in arginine and serine. This domain mediates interactions between the SR proteins and proteins within the splicing machinery. hnRNPs binds RNA and act as repressors Most silencers are recognized by hnRNP ( heterogeneous nuclear ribonucleoprotein) family. These proteins bind RNA, but lack the RS domains. Therefore, (1) They cannot recruit the splicing machinery. (2) they block the use of the specific splice sites that they bind. Regulated alternative splicing Figure 13-17 Binds at each end of the exon and conceals (隐藏) it Coats the RNA and makes the exons invisible to the splicing machinery An example of repressors: inhibition of splicing by hnRNPI Figure 13-18 选择性剪接的结果: 1. Producing multiple protein products, called isoforms. 2. Switching on and off the expression of a given gene. In this case, one functional protein is produced by a splicing pattern, and the non-functional proteins are resulted from other splicing patterns. 有一小类的内含子的剪接通过小剪接体实现 This spliceosome works on a minority of exons, and those have distinct splice-site sequence. The chemical pathway is the same as the major spliceosome. Figure 13-19 The AU-AC spliceosome U11 and U12 are in places of U1 and U2, respectively EXON SHUFFLING Topic 5:外显子重排 所有的真核基因都有内含子,而原核基因却很少有内含子. 有两个假说 : 1. Introns early model – introns existed in all organisms but have been lost from bacteria. 2. Intron late model – introns never existed in bacteria but rather arose later in evolution. 外显子的重排可以产生新基因,从而编码新蛋白 为什么真核生物要保留内含子? 内含子去除的需要,可以通过选择性剪接由单基因产生多蛋白. 2. 内含子把编码序列分成了外显子,可以通过外显子重排产生新基因(new genes). 1. The borders between exo
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