【正文】 白質(zhì)生物合成的調(diào)控 ， 就是通過(guò) mRNA本身 所固有的信號(hào)與可溶性蛋白因子或者與核糖體之間的相互作用而實(shí)現(xiàn)的 。 復(fù)習(xí)上節(jié)課所講述內(nèi)容： RNA的加工成熟： 各種基因的轉(zhuǎn)錄產(chǎn) 物都是 RNA， 無(wú)論是 rRNA、 tRNA是mRNA， 初級(jí)轉(zhuǎn)錄產(chǎn)物只有經(jīng)過(guò)加工，才能成為有生物功能的活性分子。 rRNA加工有兩個(gè)內(nèi)容？真核生物的 rRNA基因是如何轉(zhuǎn)錄的？ rRNA的化學(xué)修飾？ mRNA的加工成熟？ 真核生物基因轉(zhuǎn)錄后加工的多樣性：知道簡(jiǎn)單轉(zhuǎn)錄單位和復(fù)雜轉(zhuǎn)錄單位； 大致了解 翻譯水平的調(diào)控； 本節(jié)課所講述內(nèi)容： English Review Chapter 7。 第八章：疾病與人類健康 第一節(jié)：腫瘤與癌癥 ? 在蛋白質(zhì)生物合成的過(guò)程中 ， 特別是在起始反 應(yīng)中 ，mRNA的 “ 可翻譯性 ” 是起決定作用的 ， 其 5’ 末端的帽子結(jié)構(gòu) 、 二級(jí)結(jié)構(gòu) 、 與 rRNA的互補(bǔ)性以及起始密碼附近的核苷酸序列都是蛋白質(zhì)生物合成的信號(hào)系統(tǒng) 。 ? 蛋白質(zhì)生物合成的調(diào)控 ， 就是通過(guò) mRNA本身 所固有的信號(hào)與可溶性蛋白因子或者與核糖體之間的相互作用而實(shí)現(xiàn)的 。 English Review: Control Of Expression In Eukaryotes ? Eukaryotic genes are controlled individually and each gene has specific control sequences preceding the transcription start site Eukaryotes Have Large Complex Geneomes ? The human genome is about 3 x 109 base pairs or ≈ 1 m of DNA ? Because humans are diploid, each nucleus contains 6 x 109 base pairs or ≈ 2 m of DNA ? That is a lot to pack into a little nucleus! Eukaryotic DNA Must be Packaged ? Eukaryotic DNA exhibits many levels of packaging ? The fundamental unit is the nucleosome, DNA wound around histone proteins ? Nucleosomes arrange themselves together to form higher and higher levels of packaging. Highly Packaged DNA Cannot be Expressed ? The most highly packaged form of DNA is “heterochromatin” ? Heterochromatin cannot be transcribed, therefore expression of genes is prevented ? Chromosome puffs on some insect chomosomes illustrate where active gene expression is going on Only a Subset of Genes is Expressed at any Given Time ? It takes lots of energy to express genes ? Thus it would be wasteful to express all genes all the time ? By differential expression of genes, cells can respond to changes in the environment ? Differential expression, allows cells to specialize in multicelled anisms. ? Differential expression also allows anisms to develop over time. DNA Cytoplasm Nucleus G AAAAAA Export Degradation etc. Control of Gene Expression G AAAAAA RNA Processing mRNA RNA Transcription Translation Packaging Modification Transportation Degradation Logical Expression Control Points ? DNA packaging ? Transcription ? RNA processing ? mRNA Export ? mRNA masking/unmasking and/or modification ? mRNA degradation ? Translation ? Protein modification ? Protein transport ? Protein degradation Increasing cost The logical place to control expression is before the gene is transcribed A “Simple” Eukaryotic Gene Terminator Sequence Promoter/ Control Region Transcription Start Site 3’ 5’ RNA Transcript Introns Exon 2 Exon 3 Int. 2 Exon 1 Int. 1 3’ Untranslated Region 5’ Untranslated Region Exons 5’ DNA 3’ Enhancers Enhancer Transcribed Region 3’ 5’ TF TF 3’ 5’ TF TF 5’ RNA RNA Pol. RNA Pol. Many bases Promoter Eukaryotic mRNA Protein Coding Region 3’ Untranslated Region 5’ Untranslated Region Exon 2 Exon 3 Exon 1 AAAAA G 3’ 5’ 3’ Poly A Tail 5’ Cap ? RNA processing achieves three things: ? Removal of introns ? Addition of a 5’ cap ? Addition of a 3’ tail Regulation of Gene Expression Six steps at which eucaryotic gene expression can be regulated. DNA RNA transcript mRNA mRNA inactive mRNA protein inactive protein NUCLEUS CYTOSOL transcriptional control RNA processing control RNA transport and localization control translation control mRNA degradation control protein activity control Translational control In principle, every step required for the process of gene expression could be controlled. Predominant form: Control of initiation of transcription. ?1. Transcriptional Initiation: ?This is the most important mode for control of eukaryotic gene expression. ?promoter elements : ?enhancer sequences can enhance the activity of RNA polymerase at a given promoter by binding specific transcription factors. 2. Transcript Processing and Modification: Eukaryotic mRNAs must be capped and polyadenylated, and the introns must be accurately removed. Several genes have been identified that undergo tissuespecific patterns of alternative splicing, which generate biologically different proteins from the same gene. ?3. RNA Transport: A fully processed mRNA must leave the nucleus in order to be translated into protein. ?4. Transcript Stability: Unlike prokaryotic mRNAs, whose halflives are all in the range of 15 minutes, eukaryotic mRNAs can vary greatly in their stability. Certain unstable transcripts have sequences that are signals for rapid degradation. ?5. Translational Initiation: Since many mRNAs have multiple methionine codons, the ability of ribosomes to recognize and initiate synthesis from the correct AUG codon can affect the expression of a gene product. ?Several examples have emerged demonstrating that some eukaryotic proteins initiate at nonAUG codons. This phenomenon has been known to occur in E. coli for quite some time, but only recently has it been observed in eukaryotic mRNAs. ?6. PostTranslational Modification: Common modifications include glycosylation, acetylation, fatty acylation, disulfide bond formations, etc. ?7. Protein Transport: proteins must be biologically active following translation and processing, they must be transported to their site of action. ?8. Control of Protein Stability: Many proteins are rapidly degraded, whereas others are highly stable. Specific amino acid sequences in some proteins have been shown to bring about rapid degradation Control of Eukaryotic Transcription Initiation ?Transcription of the different classes of RNAs in eukaryotes is carried out by three differ